Cherubism in Saudi population: a rare case report / Querubismo na população Saudi: relato de um caso raro

Cherubism is a rare hereditary benign fibro-osseous disorder characterised by bilateral swelling of the mandible and/or maxilla with varying severity of involvement. It occurs because of dominant mutations in SH3BP2 gene on the chromosome 4p16.3. On radiography cherubic lesions appear as multilocular cystic radiolucencies in the jaw bones giving a soap bubble appearance. These lesions usually heal by themselves by the time the patient attains puberty. Treatment is necessary only in aggressive cases where there is severe facial deformity or vital functions are hampered. Surgical corrections are preferred when the lesion is in its dormant phase. The aim of the present case report is to illustrate a case of cherubism in a 9-year-old Saudi boy which is a very rare occurrence as only 1 case of cherubism has been reported so far in the Saudi Arabian population (AU)

Querubismo é uma desordem fibro-óssea hereditária rara caracterizada por aumento de volume bilateral da mandíbula e/ou maxila com graus variáveis de severidade. Ocorre devido a mutação dominante no gene SH3BP2 no cromossomo 4p16.3. Radiograficamente as lesões de querubismo aparecem como radiolucência multilocular semelhantes a bolhas de sabão nos ossos maxilares. Geralmente as lesões involuem espontaneamente quando o paciente atinge a puberdade. O tratamento se faz necessário apenas nos casos mais agressivos que demonstram deformidade facial severa ou comprometimento de funções vitais. Correções cirúrgicas são preferíveis quando a lesão está na fase dormente. O objetivo do presente relato é ilustrar um caso de querubismo em um paciente de 9 anos da Arábia Saudita, sendo este um evento raríssimo com apenas um outro caso relatado na população da Arábia Saudita (AU)

Alterações sistêmicas na assinatura do ciclo celular de pacientes com COVID-19 / Systemic changes in the cell cycle signature of patients with COVID-19

Com base nas perturbações fosfoproteômicas de moléculas associadas ao ciclo celular em células infectadas pelo coronavírus causador da síndrome respiratória aguda grave (SARSCoV)-2, a hipótese de inibidores do ciclo celular como uma terapia potencial para a doença de coronavírus 2019 (COVID-19) foi proposta. No entanto, o cenário das alterações do ciclo celular em COVID-19 permanece inexplorado. Aqui, realizamos uma análise integrativa de sistemas imunológicos de proteoma publicamente disponível (espectrometria de massa) e dados de transcriptoma (sequenciamento de RNA em massa e de célula única [scRNAseq]), com o objetivo de caracterizar mudanças globais na assinatura do ciclo celular de pacientes com COVID-19. Além de módulos de co-expressão de genes significativos enriquecidos associados ao ciclo celular, encontramos uma rede interconectada de proteínas diferencialmente expressas associadas ao ciclo celular (DEPs) e genes (DEGs) integrando dados moleculares de 1.480 indivíduos (974 pacientes infectados por SARS-CoV-2 e 506 controles [controles saudáveis ou indivíduos com outras doenças respiratórias]). Entre esses DEPs e DEGs estão várias ciclinas (CCNs), ciclo de divisão celular (CDCs), quinases dependentes de ciclinas (CDKs) e proteínas de manutenção de minicromossomos (MCMs). Embora os pacientes com COVID-19 compartilhem parcialmente o padrão de expressão de algumas moléculas associadas ao ciclo celular com outras doenças respiratórias, eles exibiram uma expressão significativamente maior de moléculas associadas ao ciclo celular relacionadas à gravidade da doença. Notavelmente, a assinatura do ciclo celular predominou nos leucócitos do sangue dos pacientes, mas não nas vias aéreas superiores. Os dados de scRNAseq de 229 indivíduos (159 pacientes com COVID- 19 e 70 controles) revelaram que as alterações das assinaturas do ciclo celular predominam nas células B, T e NK. Esses resultados fornecem uma compreensão global única das alterações nas moléculas associadas ao ciclo celular em pacientes com COVID-19, sugerindo novas vias putativas para intervenção terapêutica

Based on phosphoproteomics perturbations of cell cycle-associated molecules in severe acute respiratory syndrome coronavirus (SARS-CoV)-2-infected cells, the hypothesis of cell cycle inhibitors as a potential therapy for Coronavirus disease 2019 (COVID-19) has been proposed. However, the landscape of cell cycle alterations in COVID-19 remains mostly unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome (mass spectrometry) and transcriptome data (bulk and single-cell RNA sequencing [scRNAseq]), aiming to characterize global changes in the cell cycle signature of COVID-19 patients. Beyond significant enriched cell cycle-associated gene co-expression modules, we found an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating molecular data of 1,480 individuals (974 SARS-CoV- 2 infected patients and 506 controls [either healthy controls or individuals with other respiratory illness]). Among these DEPs and DEGs are several cyclins (CCNs), cell division cycle (CDCs), cyclin-dependent kinases (CDKs), and mini-chromosome maintenance proteins (MCMs). Although COVID-19 patients partially shared the expression pattern of some cell cycleassociated molecules with other respiratory illnesses, they exhibited a significantly higher expression of cell cycle-associated molecules associated with disease severity. Notably, the cell cycle signature predominated in the patients blood leukocytes but not in the upper airways. The scRNAseq data from 229 individuals (159 COVID-19 patients and 70 controls) revealed that the alterations of cell cycle signatures predominate in B, T, and NK cells. These results provide a unique global comprehension of the alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention

9p21 Locus Polymorphisms: Risk and Severity Factors of Coronary Artery Disease in Venezuelan Patients

Abstract Background: The 9p21 region is the most relevant locus associated with coronary heart disease in different populations. However, there are no studies that prove that this region is a risk factor in the Venezuelan population. Objectives: To analyze whether or not the 9p21 rs1333049 polymorphism is a risk factor for acute myocardial infarction (AMI) in Venezuelan patients, as well as to investigate its correlation with cardiovascular risk factors (CVRF), age of occurrence, type and severity of infarction, and the correlation of the rs10757274 polymorphism with severity of coronary artery disease. Methods: This was an association study, including 487 unrelated Venezuelan individuals, grouped in 354 patients with AMI and 133 controls. The rs1333049 and rs10757274 polymorphisms were determined using the polymerase chain reaction (PCR) technique with sequence-specific primers. The analysis of association was determined using the SNPStats tool. The continuous variable description and the correlations were performed using the SPSS statistical software. Significance was established at p<0.05. Results: A positive correlation was observed between the rs1333049 polymorphism and the presence of hypertension ( r: 0.145, p: 0.006), and between hypertension and heart infarction ( r: 0.318, p: <0.0001). A positive correlation was found between the rs10757274 polymorphism and the number of coronary vessels that presented obstructive lesions in patients aged ≤ 55 years ( r: 0.276, p: 0.0078). Conclusion: The rs1333049 polymorphism at the 9p21 locus is correlated with hypertension in Venezuelan patients, while the rs10757274 polymorphism is associated with the progression of coronary atherosclerosis, suggested by the correlation with the number of coronary vessels that presented significant obstructive lesions.

Síndrome de insensibilidad completa a andrógenos / Complete androgen insensitivity syndrome

El síndrome de insensibilidad a los andrógenos (SIA), conocido también como un síndrome de feminización testicular, incluye un grupo variado de mutaciones que se relacionan con la disfunción de los receptores de andrógenos y la resistencia de los tejidos diana a la acción de las hormonas masculinas. Es causado por alteraciones genéticas localizadas en la secuencia de codificación de los receptores de andrógenos ligada al cromosoma Xq11 - 12, el gen que codifica al receptor de los andrógenos, de un individuo genéticamente masculino (46 XY). Las formas clínicas moderada, parcial o completa, dependen del grado de insensibilidad androgénica. Los avances en las causas genéticas han permitido que estas condiciones congénitas de desarrollo del sexo cromosómico, gonadal o anatómico atípico sean denominados trastornos de diferenciación sexual

Androgen insensitivity syndrome (AIS), also known as testicular feminization syndrome, includes a diverse group of mutations that are related to androgen receptor dysfunction and resistance of target tissues to the action of hormones masculine. It is caused by localized genetic alterations in the androgen receptor coding sequence linked to chromosome Xq11-12, the gene encoding the androgen receptor, of a genetically male (46 XY) individual. Moderate, partial, or complete clinical forms depend on the degree of androgen insensitivity. Advances in genetic causes have allowed these congenital conditions of atypical chromosomal, gonadal, or anatomical sex development to be called disorders of sexual differentiation

Tracking the evolutionary pathways among Brazilian Lebiasina species (Teleostei: Lebiasinidae): a chromosomal and genomic comparative investigation

Despite several difficulties in chromosomal analyses of small-sized fishes, the cytogenetics of the Lebiasinidae was largely improved in the last years, showing differential patterns in the chromosomal evolution inside the family. In this context, it has been shown that genus Lebiasina preserves its karyotypic macrostructure, composed of 2n = 36 chromosomes, whereas the other genera generally present higher 2n. This study focused on the comparative cytogenetics of three Lebiasina species, one of them analyzed here for the first time, using conventional and molecular procedures. The results reinforced the differentiated evolutionary path of the genus Lebiasina while, at the same time, highlighted the genomic particularities that have accompanied the evolution of each species. In this sense, the repetitive components of the genome played a significant role in the differentiation of each species. It is also notable that L. minuta and L. melanoguttata, the two species that occur exclusively in the Brazilian territory, show greater chromosomal similarities to each other than to the trans-Andean sister species, L. bimaculata.(AU)

Apesar das dificuldades encontradas em se realizar análises cromossômicas em peixes de pequeno porte, os estudos citogenéticos em Lebiasinidae vêm crescendo nos últimos anos e demonstrando padrões diferenciados na evolução cromossômica entre os membros da família. Nesse contexto, o gênero Lebiasina tem mostrado preservar sua macroestrutura cariotípica, composta por 2n = 36 cromossomos, enquanto os demais gêneros geralmente apresentam 2n maiores. Este estudo tem como foco a citogenética comparativa de três espécies de Lebiasina, sendo uma delas analisada pela primeira vez aqui, através do emprego de técnicas convencionais e moleculares. Os resultados obtidos reforçam a trajetória evolutiva diferenciada do gênero Lebiasina, ao mesmo tempo em que evidenciam as particularidades genômicas que acompanham a evolução de cada uma das espécies. Neste contexto, os componentes repetitivos do genoma tiveram um papel importante na caracterização particular de cada uma das espécies. Também, é notável que L. minuta e L. melanoguttata, duas espécies que ocorrem exclusivamente no território brasileiro, apresentam maior proximidade citogenética entre elas do que com a espécie irmã transandina, L. bimaculata.(AU)

Searching chromosome mosaicisms in 45, X Turner syndrome: how relevant is it?

ABSTRACT Objective: To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS). Materials and methods: FISH and PCR were performed for the presence of chromosome mosaicism and Y-derived-material and genetic findings were correlated to clinical data. Results: Thirty-one participants were enrolled: 18 (58%) had chromosome mosaicisms (FISH), Y-derived material was found in 2. Yet, SRY primer was found with PCR in only one of them and DYZ3 was not found. The most frequent clinical findings were short or webbed neck (81,82%), high-arched palate (78%), breast hypertelorism, e cubitus valgus and genu valgus (57.6%, both), short fourth metacarpals (46.9%), epicanthic folds (43.8%), shield chest (43.8%), lymphedema (37.5%), and low set ears (34.4%). Both patients with Y-derived-material had primary amenorrhea, dyslipidemia and reached the height of 150 cm despite not treated with recombinant growth hormone (GHr). One of them showed 26% of leukocytes with Y-derived material and few clinical findings. Conclusions: FISH techniques proved efficient in detecting chromosome mosaicisms and Y-derived material and searching in different tissues such as mouth cells is critical due to the possibility of tissue-specific mosaicism. Phenotypical variance in TS may be a signal of chromosome mosaicisms, especially with the presence of Y-derived material.

Cytogenetic and molecular characterization of an SRY-negative 46, XX ovotesticular DSD: a case report / Caracterização citogenética e molecular de um DDS ovotesticular 46, XX SRY-negativo: relato de caso

Introduction: Ovotesticular disorder of sex development is a rare condition characterized by the concomitant presence of testicular and ovarian tissue, and usually presents genital ambiguity. They are chromosomally heterogeneous, and cytogenetic analyses is relevant. Objective: to report a patient from Manaus, Amazonas state, Brazil, with ovotesticular disorder of sex differentiation 46,XX and SRY-negative. Case report: patient aged 19 years, first child of non-consanguineous parents, diagnosed at birth with genital ambiguity and, without correct diagnosis, was registered a male sex. The patient underwent surgery to correct bilateral cryptorchidism, orchiopexy and colpectomy. During puberty, he developed female and male sexual characteristics. Investigation at this time revealed: laboratory (normal total testosterone and estradiol as high follicle-stimulating hormone and luteinizing hormone, histopathological (right gonad, ovarian follicles and left gonad, atrophic testicles), karyotype (46, XX) and molecular (SRY-negative). Diagnosis of ovotesticular disorder of sex development was established. The patient chose to remain male and underwent bilateral mastectomy, vaginal colpectomy and bilateral gonadectomy. Currently, the patient receives hormonal replacement therapy, followup with a multi-professional approach and awaits masculinizing genitoplasty. Discussion: For OT-DSD individuals with 46, XX, the female sex is suggested as the best sex of rearing option. Unlike the reported cases, the patient chose the male sex, since the sex at registration of birth was important in his choice. Conclusion: Cytogenetic and molecular analyses allowed us to assist in the etiological diagnosis of the patient with OT-DSD. However, molecular analyses are necessary to elucidate the genes involved in the sexual determination of this patient.

Introdução: distúrbio da diferenciação do sexo ovotesticular é uma condição rara com presença concomitante de tecido testicular e ovariano, geralmente com ambiguidade genital. Os pacientes são cromossomicamente heterogêneos e a análise citogenética é fundamental. Objetivo: relatar o caso de um paciente do município de Manaus, Amazonas, portador de distúrbio da diferenciação do sexo ovotesticular 46, XX e SRY-negativo. Caso clínico: paciente de 19 anos, primeiro filho de pais não consanguíneos, que ao nascimento foi diagnosticado com ambiguidade genital, contudo, sem diagnóstico correto, foi registrado como sendo do sexo masculino. Foi submetido a cirurgias para correção da criptoquirdia bilateral, orquidopexia e colpectomia vaginal. Na puberdade, desenvolveu características sexuais feminina e masculina. Investigação diagnóstica mostrou: exames hormonais (testosterona total e estradiol normais enquanto hormônio folículo-estimulante e hormônio luteinizante elevados), histopatológicos (gônada direita, folículos ovarianos e gônadas esquerda, testículos atróficos), cariótipo (46, XX) e molecular (SRY-negativo). O diagnóstico de distúrbio da diferenciação do sexo ovotesticular foi estabelecido. O paciente optou por permanecer no sexo masculino e submeteuse à mastectomia bilateral, colpectomia vaginal e gonadectomia bilateral. Atualmente faz reposição hormonal, acompanhamento com abordagem multiprofissional e aguarda pela genitoplastia masculinizante. Discussão: aos indivíduos DDS-OT com 46, XX é sugerido como a melhor opção de sexo, o feminino. Diferentemente dos casos relatados, o paciente optou por permanecer no sexo masculino, visto que o registro de nascimento foi importante para a sua escolha. Conclusão: análises citogenéticas e moleculares permitiu auxiliar no diagnóstico etiológico do paciente com DDS-OT, contudo, análises moleculares são necessárias para elucidação de genes envolvidos na determinação sexual desse paciente.

Effects of trichostatin A on FHIT and WWOX genes expression, cell growth inhibition and apoptosis induction in hepatocellular carcinoma WCH 17 cell line

Previously, we evaluated the effect of trichostatin A (TSA) on the expression of DNA methyltransferase 1 (DNMT1) in Hepatocellular Carcinoma (HCC). Fragile histidine triad (FHIT) and WW domain-containing oxidoreductase (WWOX) are two of the most common down-regulated genes in many cancers located on chromosome 3p14.2 and 16q23.3-24.1 respectively. The aim of the current study was to assess the effect of TSA on these genes expression, cell growth, and apoptosis in HCC WCH 17 cell. The cells were seeded and treated with TSA at different times. Then, MTT assay, flow cytometry, and qRT-PCR were achieved to determine viability, apoptosis and gene expression respectively. Cell growth was significantly inhibited, 92 to 36% after 24 h, 86 to 28% after 48 h, and 78 to 24% after 72 h. The results of flow cytometry confirmed that TSA increased apoptosis compared to the control group, the apoptosis percentage increased to 12%, 16%, and 18% in comparison to control groups (2%). Significant up-regulation of the genes was observed in all treated groups. We concluded that re-expression of silenced WWOX and FHIT genes could be achieved by TSA resulting in cell growth inhibition and apoptosis induction in WCH 17 cell.

Occurrence of euchromatic B chromosomes in natural populations of Moenkhausia bonita and M. forestii (Pisces: Characidae)

Moenkhausia is a highly specious genus among the Characidae, composed of 96 valid species. Only twelve species have a known karyotype. Thus, here are presented the first cytogenetic data of two allopatric populations of Moenkhausia bonita and one of M. forestii, both belonging to the upper Paraná River basin (PR) with discussion on the evolutionary and cytotaxonomic aspects of the genus. The two species presented 2n = 50 chromosomes but different karyotype formulas and occurrence of 1-2 B chromosomes. These elements are small metacentrics in M. bonita and small acrocentrics in M. forestii. In both species, B chromosomes were euchromatic. Ag-NOR sites were found in pair 3 (metacentric), coinciding with fluorescent in situ hybridization (FISH) by the 18S rDNA probe in both species. However, the species differed in terms of the number and position of 5S rDNA sites. Heterochromatic blocks, mapped in M. bonita showed the least amount of heterochromatin in the terminal and pericentromeric regions, while the M. forestii karyotype revealed a greater amount of interstitial heterochromatic blocks. The karyotype distinctions between the two species, including the morphology of B chromosomes, may contribute as a reference in the taxonomic studies in this group.(AU)

Moenkhausia é um gênero altamente especioso dentre os Characidae, composto por 96 espécies válidas, mas apenas doze espécies têm seus cariótipos conhecidos. Portanto, são apresentados aqui os primeiros dados citogenéticos de duas populações alopátricas de Moenkhausia bonita e uma de M. forestii, ambas pertencentes à bacia do alto rio Paraná (PR), com uma ampla discussão sobre os aspectos evolutivos e citotaxonômicos do gênero. As duas espécies apresentaram 2n = 50 cromossomos, mas diferentes fórmulas cariotípicas e ocorrência de 1-2 cromossomos B. Esses elementos são pequenos metacêntricos em M. bonita e acrocêntricos pequenos em M. forestii. Em ambas as espécies, os cromossomos B apresentaram-se eucromáticos. Sítios Ag-NOR foram encontrados no par 3 (metacêntrico), coincidindo com a hibridização fluorescente in situ (FISH) pela sonda 18S rDNA em ambas as espécies. No entanto, as espécies diferiram em termos de número e posição dos sítios de 5S rDNA. Blocos heterocromáticos mapeados em M. bonita revelaram pequena quantidade de heterocromatina nas regiões terminal e pericentromérica, enquanto o cariótipo de M. forestii revelou uma maior quantidade de blocos heterocromáticos intersticiais. As distinções cariotípicas entre as duas espécies, incluindo a morfologia dos cromossomos B, podem contribuir como uma referência em estudos taxonômicos neste grupo.(AU)

Tipificación del cassette cromosómico estafilocócico de Staphylococcus aureus resistentes al meticilino en el estado de Aragua, Venezuela / Typification of the staphylococcal chromosome cassette of methicillin-resistant Staphylococcus aureus in the state of Aragua, Venezuela

RESUMEN Objetivos: Tipificar el casette SCCmec en cepas de Staphylococcus aureus resistentes a meticilino (SARM) en aislados clínicos de centros de salud del Estado Aragua-Venezuela y comparar la presencia de los genotipos SCCmec entre los centros de salud del estado y según el tipo de infección. Materiales y métodos: Durante enero y agosto de 2015 se estudiaron 81 cepas SARM de cuatro centros de salud del estado de Aragua en Venezuela. La resistencia al meticilino se midió con el método de Kirby-Bauer con discos de oxacilina (1 µgr) y cefoxitina (30 µgr). El gen mecA y el SCCmec se analizaron por la técnica de reacción en cadena de polimerasa múltiple. Resultados: 55 aislados (67,9%) amplificaron el gen mecA, y 24 cepas (43,6%) amplificaron el SCCmec. El SCCmec I fue el más frecuente, seguido de SCCmecIV y SCCmec III, representaron el 62,5%, 25% y 12,5%, respectivamente. El SCCmec I fue predominante en el centro de salud A (80%), mientras que el SCCmec IV se encontró en el centro de salud B (60%) y C (100%). En el centro de salud D, 50% resultó ser SCCmec I y 50% SCCmec IVd. Se encontró relación entre el SCCmec y el centro de salud con significancia estadística. En infecciones de piel y tejidos blandos y en las respiratorias predominó el SCCmec I con 63,2% y 50% respectivamente. Conclusiones: La frecuencia de SCCmec I y IV permitirá establecer nuevas medidas en el uso y control de la resistencia a los antibióticos.

ABSTRACT Objective: Typify the SCCmec cassette in methicillin-resistant strains of Staphylococcus aureus in clinical isolates from health centers in the State of Aragua-Venezuela and compare the presence of SCCmec genotypes among the state health centers and according to the type of infection. Materials and methods: 81 MRSA strains from four health centers of the Aragua-Venezuela State were studied. Methicillin resistance was performed with the Kirby-Bauer method with oxacillin (1 µg) and cefoxitin (30 µg) disks. The mecA gene and SCCmec were analyzed by the multiple PCR technique. Results: Only 55 isolates (67.9%) amplified the mecA gene, and 24 strains (43.6%) amplified SCCmec. SCCmec type I was the most frequency, followed by SCCmec IV and SCCmec III, representing 62.5%, 25% and 12.5%, respectively. SCCmec I was predominant in health center A (80%), while in B and C 60% and 100% respectively were SCCmec IV. At health center D, 50% turned out to be SCCmec I and 50% SCCmec IVd. A relationship was found between the SCCmec and the health center with statistical significance. SCCmec I predominated in skin and soft tissue and respiratory infections with 63.2% and 50%, respectively. There was no association between genotype and type of infection with a p value greater than 0.05. Conclusions: The prevalence of SCCmec I and IV will allow establishing new measures in the use of antibiotics and epidemiological control.

Resultados después de la implementación del test de DNA fetal libre circulante en sangre materna (DNA-lc) para cribado de cromosomopatías fetales / Results after the implementation of the cell-free fetal DNA test in maternal plasma (cfDNA) in screening for fetal aneuploidies

Objetivo: Evaluar la disminución de la tasa de técnicas invasivas de diagnóstico prenatal tras la introducción del cribado contingente de cromosomopatías con test de DNA fetal libre circulante (DNA-lc)y demostrar que este método de cribado es coste-efectivo. Método: estudio observacional prospectivo y estudio de coste efectividad. Primero se describen los resultados del cribado combinado en dos tiempos de primer trimestre desde febrero de 2008 a junio 2018 diez primeros años del hospital): 21744 cribados realizados de un total de 23000 partos. En abril de 2016 se implementa un modelo de cribado contingente de cromosomopatías con test de DNAlc (se oferta el test a pacientes con resultado de riesgo intermedio en el cribado combinado). En segundo lugar se analizan los resultados tras la implementación del test y se comparan dos períodos de tiempo con y sin cribado contingente (año 2015 con el período abril 2016 hasta marzo de 2019). Resulta-dos: disminución total de las técnicas invasivas del 54% por disminución de la tasa de amniocentesis, manteniéndose constante la tasa de biopsias coriales. La tasa de pérdidas fetales por técnica invasiva alcanza el 0%. Usamos seis indicadores de calidad para evaluar el test. Se hanahorrado 70200 euros con la implementación del test de DNA-lc. Discusión: el test de DNAlc resulta útil en el cribado contingente de cromosomopatías porque reduce la tasa de amniocentesis por indicación de alto riesgo y además es coste efectivo. El cribado combinado de primer trimestre es la técnica de elección para el cribado de aneuploidias. El test de DNAlc no puede sustituir al cribado combinado porque es caro, pero resulta muy útil si se realiza cribado contingente a la población seleccionada de riesgo intermedio.

Velocidad de crecimiento en pacientes con síndrome de Turner que recibieron hormona recombinante de crecimiento / Growth rate in patients with Turner syndrome who received recombinant growth hormone

El síndrome de Turner (ST) afecta a uno de cada 2000-2500 recién nacidos vivos y tiene una prevalencia de 50 por cada 100 000 mujeres. Las manifestaciones clínicas son variables, dependiendo del tipo de alteración cromosómica y de la edad de presentación. Una de las características más prevalentes y sobresalientes del síndrome es su estatura extremadamente baja. La hormona de crecimiento humana recombinante (rh-GH) se ha usado para aumentar el crecimiento y la estatura final en las niñas que tienen el síndrome de Turner. Para valorar los efectos de la hormona de crecimiento recombinante en las niñas y adolescentes con ST, hemos tomado en cuenta el efecto de la hGH, considerando la velocidad en la talla de crecimiento como un punto importante del estudio observacional retrospectivo. Resultados principales: El uso de rh-GH tiene una relación estadísticamente significativa (p0.049 <0.05), que se asocia con un factor de influencia positiva en relación con la velocidad de crecimiento, como variable principal. Al comparar a las pacientes que recibieron la hormona de crecimiento con las que no la recibieron, en las primeras existe la tendencia a acercarse a la curva del percentil 10 en comparación con la de aquellas que no recibieron la rh-GH, que estuvieron más lejos de la curva.

Turner syndrome (TS) affects about one in 1500 to 2500 live-born females. One of the most prevalent and salient features of the syndrome is extremely short stature. Recombinant human growth hormone (rh-GH) has been used to increase growth and final height in girls who have Turner syndrome. To assess the effects of recombinant growth hormone in children and adolescents with TS we have evaluated the effect of HGH considering growth rate as an important point through a retrospective observational study. Main results: The use of rh-GH has a statistically significant relationship (p0.049 <0.05) that is associated with an influencing factor in favor of the use of rh-GH in relation to the variable growth rate. When comparing the patients who received growth hormone with those who did not receive, there is the tendency to arrive closer to the 10th percentile curve compared to the curve of the patients who did not receive rh-GH, which is further away.

Genómica Social: Relaciones entre teoría de la mente y cariotipo en mujeres con diagnóstico de Síndrome de Turner / Social Genomics: Relationships between theory of mind and karyotype in women diagnosed with Turner Syndrome

La teoría de la mente refiere a la capacidad cognitiva de atribuir mente a los demás y de predecir y comprender su comportamiento en términos de entidades mentales como creencias, deseos e intenciones. Investigaciones recientes sugieren una distinción entre una teoría de la mente afectiva y una cognitiva, asignándoles un sustrato neuroanatómico específico. El Síndrome de Turner es un trastorno genético determinado por la deleción total o parcial del cromosoma X en el sexo femenino. Dadas las características biológicas, psicológicas y sociales encontradas en estas mujeres, pueden ser consideradas como una población relevante para el estudio de la teoría de la mente según parámetros biológicos como la expresión diferencial de los genes del cromosoma X. Objetivos y métodos: los objetivos de este estudio fueron describir la teoría de la mente cognitiva y afectiva en 22 mujeres con diagnóstico de Síndrome de Turner y determinar si existen perfiles distintivos de teoría de la mente asociados al cariotipo. Resultados y discusión: Los resultados indicaron que las mujeres con diagnóstico de Síndrome de Turner presentan dificultades generales en teoría de la mente, observándose un menor rendimiento en el aspecto cognitivo de esta capacidad. Asimismo, se encontró que un mayor daño genético se encuentra relacionado a mayores dificultades en la teoría de la mente cognitiva, vinculada a zonas corticales de procesamiento no automático

Theory of mind refers to the cognitive ability to attribute mind to others, and to predict and understand their behavior in terms of mental entities such as beliefs, desires and intentions. Recent research suggests a distinction between an affective and a cognitive theory of mind, assigning a specific neuroanatomical substrate to each one. Turner Syndrome is a genetic disorder that only affects women, and it's determined by a partial or complete deletion of the X-chromosome. Given the biological, psychological and social characteristics found in these women, they can be considered as a relevant population for the study of theory of mind according to biological parameters such as differential expression of the X-chromosome genes. Aims and methods: The aims of this study were to describe cognitive and affective theory of mind in 22 women diagnosed with Turner Syndrome and to determine if there are distinctive theory of mind profiles depending on the karyotype. Results and discussion: Results indicated that women diagnosed with Turner Syndrome present general difficulties in theory of mind, showing a lower performance on the cognitive aspect of this ability. Additionally, evidence was found suggesting that a greater genetic damage is related to greater difficulties in cognitive theory of mind, which is linked to cortical areas of non-automatic processing.

Concomitance of numerical chromosomal alterations with structural in an elderly with Alzheimer's disease: a case report / Concomitância de alterações cromossômicas numéricas com estruturais em idoso com doença de Alzheimer: relato de caso

AIMS: To report the first case the concomitance of numerical chromosomal abnormalities with structural as well as chromosomal abnormalities structural in a patient diagnosed with Alzheimer disease in Manaus/Amazonas. CASE DESCRIPTION: A male patient with 76 years of age was diagnosed with diagnosis of cognitive disorder- Alzheimer's disease with late onset - temporal variant after laboratory, physical and imaging exams. Cytogenetic analysis was requested for this patient, revealing the presence the concomitant of numerical and structural chromosomal abnormalities with metaphase cells composed of 45 chromosomes with the loss of one of the homologues of chromosome 21 (monosomy) and a deletion of the long arm of one of the homologues of chromosome 1 [45, XY, -21, del (1) (q?)] and metaphase cells containing 46 chromosomes with a deletion of the long arm of one of the homologues of chromosome 15 [(46, XY, del (15) (q?)]. Currently, the patient is in outpatient treatment for maintenance and control of the disease. CONCLUSIONS: Our study has underlined that karyotyping is one of the fundamental investigations for patients with Alzheimer's disease. It highlighted, in the form of a chromosomal abnormality, may have been the risk factor in Alzheimer's disease.

OBJETIVOS: Relatar o primeiro caso de concomitância de anormalidade cromossômica numérica com anormalidade cromossômica estruturais em um paciente diagnosticado com doença de Alzheimer em Manaus/Amazonas DESCRIÇÃO DO CASO: Um paciente do sexo masculino com 76 anos de idade foi diagnosticado com distúrbio cognitivo - doença de Alzheimer com início tardio - variante temporal, após exames laboratoriais, físicos e de imagem. Análises citogenéticas foi solicitado para esse paciente, revelando a presença concomitante de anormalidades cromossômicas numéricas e estruturais com células metafásicas compostas por 45 cromossomos, com a perda de um dos homólogos do cromossomo 21 (monossomia) e a deleção do braço longo de um dos homólogos do cromossomo 1 [45, XY, -21, del (1) (q?)] e células metafásicas contendo 46 cromossomos apresentando deleção no braço longo de um dos homólogos do cromossomo 15 [(46, XY, del (15) (q?)] Atualmente, o paciente encontra-se em tratamento ambulatorial para manutenção e controle da doença. CONCLUSÕES: Nosso estudo revelam que a cariotipagem é uma das investigações fundamentais para pacientes com doença de Alzheimer. A anormalidade cromossômicas pode ter sido o fator de risco para a doença de Alzheimer.

Development and characterization of polyclonal antibodies against the linker region of the telomere-binding protein TRF2

Background: TRF2 (telomeric repeat binding factor 2) is an essential component of the telomere-binding protein complex shelterin. TRF2 induces the formation of a special structure of telomeric DNA and counteracts activation of DNA damage-response pathways telomeres. TRF2 has a poorly characterized linker region (udTRF2) between its homodimerization and DNA-binding domains. Some lines of evidence have shown that this region could be involved in TRF2 interaction with nuclear lamina. Results: In this study, the fragment of the TERF2 gene encoding udTRF2 domain of telomere-binding protein TRF2 was produced by PCR and cloned into the pET32a vector. The resulting plasmid pET32a-udTRF2 was used for the expression of the recombinant udTRF2 in E. coli RosettaBlue (DE3). The protein was isolated and purified using ammonium sulfate precipitation followed by ion-exchange chromatography. The purified recombinant protein udTRF2 was injected into guinea pigs to generate polyclonal antibodies. The ability of anti-udTRF2 antibodies to bind endogenous TRF2 in human skin fibroblasts was tested by western blotting and immunofluorescent staining. Conclusions: In this study, the recombinant protein udTRF2 and antibodies to it were generated. Both protein and antibodies will provide a useful tool for investigation of the functions of the udTRF2 domain and its role in the interaction between TRF2 and nuclear lamina.

Polyploidy as a chromosomal component of stochastic noise: variable scalar multiples of the diploid chromosome complement in the invertebrate species Girardia schubarti from Brazil / Poliploidia como componente cromossômico de ruído estocástico: variações escalares múltiplas do componente cromossômico diploide do invertebrado Girardia schubarti ocorrente no Brasil

Abstract Chromosome stoichiometry, a form of genetic plasticity, specifically refers to variation in the standard diploid genomic composition of an individual or species. In the present work, freshwater planarians (Girardia schubarti) were analyzed to recognize variations in chromosomal stoichiometry especially of complete ploidal change between specimens, within specimens and between cells within specimens and any relations they might have with selected components of phenotypic plasticity. Homoploid polyploids for the group reached rational scalar multiples (e.g. tetraploids) or irrational scalar multiples (e.g. triploids). Karyotypic mosaics emerged where individual cells presented polyploid multiples in arithmetic and geometric progressions. Ploidal multiplicity, a chromosomal component of stochastic noise, had positive phenotypic effects (increased dimensions) on morphologic criteria of body length, body width and dorsal surface reflecting a significant genotypic plasticity (GP) and robust phenotypic plasticity (PP). Variable but significant association of genotypic plasticity with robust phenotypic variance suggests kinetics of phenotypic homeostasis that is species-specific permitting phenotypic adaptability to environmental variables by means of GP. That association is diminished, deactivated or lost in more advanced and more complex organisms.

Resumo A estequiometria cromossômica, uma forma de plasticidade genotípica, representa variações na composição genômica diploide de um indivíduo ou espécie. Planárias límnicas (Girardia schubarti) foram analisadas para verificar a estequiometria cromossômica, especialmente alterações na ploidia entre espécimes, em cada espécime e entre células do mesmo espécime, além de relações dessas alterações com a plasticidade fenotípica. Espécimes poliploides homoploides apresentaram múltiplos escalares racionais ou irracionais, tais como triploides. Mosaicos cariotípicos ocorreram quando células apresentaram poliploides múltiplos em progressões aritméticas e geométricas. Nas planárias estudadas, a multiplicidade ploidal, um componente cromossômico de ruído estocástico, apresentou efeitos fenotípicos positivos, causando aumento das dimensões dos indivíduos, tais como comprimento corporal, largura do corpo e superfície dorsal, indicando plasticidade genotípica (GP) significativa e plasticidade fenotípica (PP) robusta. Associações significativas da plasticidade genotípica com variâncias fenotípicas robustas, embora variáveis, sugerem que a homeostase fenotípica, a qual é espécie-específica, possibilita adaptações a variáveis ambientais através da GP. Tal associação apresenta-se reduzida, desativada ou perdida em organismos mais complexos.

Incontinencia Pigmenti: rara genodermatosis ligada con el cromosoma X. Reporte de un caso clínico / Incontinentia pigmenti: a rare X-linked genodermatosis. A case report / Incontinência pigmenti: rara genodermatose ligada com o cromossoma x. Reporte de um caso clínico

La incontinencia pigmenti (síndrome de Bloch-Sulzberger) es una genodermatosis rara causada por una mutación en el gen NEMO localizado en el cromosoma X. Las manifestaciones cutáneas son marcadoras de esta entidad y se dan de forma temprana y cronológica. El compromiso extra cutáneo se da hasta en el 80% de los casos y las alteraciones neurológicas y oftalmológicas son marcadores del pronóstico porque tienen el potencial de producir secuelas irreversibles. Se presenta el caso de una paciente que desde el primer día de vida inició con lesiones cutáneas que, con la evolución, desarrollaron características clásicas de una incontinencia pigmenti. Se resalta el antecedente familiar asociado, el compromiso neurológico extenso y la importancia de un manejo multidisciplinario.

Incontinentia pigmenti (Bloch-Sulzberger Syndrome) is a rare genodermatosis. The disease is X-linked and the most common molecular defect includes mutations in the NEMO gene on chromosome Xq28 in approximately 70% of patients. It is characterized by a multisystem compromise in which the skin manifestations occur in all patients. Also, the dermatological findings occur early and in chronological order. The prevalence of extra skin compromise is approximately 80% of patients. The ophthalmological and neurological manifestations are the major cause of disability in patients and may have a great impact on the quality of life. Some of damages are irreversible. We present the clinical case of a child on her first day of life. It began with skin manifestations typical of incontinentia pigmenti and extensive neurological involvement. In addition, the family history includes a sister with the disease. A multidisciplinary approach is necessary to care for patients and to detect and prevent long-term complications.

A incontinência pigmenti (síndrome de Bloch-Sulzberger) é uma genodermatose rara causada por uma mutação no gene NEMO localizado no cromossoma X. As manifestações cutâneas são marcadoras desta entidade E se dá de forma precoce e cronológica. O compromisso extra cutâneo se dá até em 80% dos casos e as alterações neurológicas e oftalmológicas são marcadores do prognóstico porque tem o potencial de produzir sequelas irreversíveis. Se apresenta o caso de uma paciente que desde o primeiro dia de vida iniciou com lesões cutâneas que, com a evolução, desenvolveram características clássicas de uma incontinência pigmenti. Se ressalta o antecedente familiar associado, o compromisso neurológico extenso e a importância de um manejo multidisciplinar.

Abordaje inmunológico del síndrome por deleción 22q11 / Immunological approaches to 22q11 deletion syndrome

El síndrome por deleción 22q11 (SD22q11) es el síndrome por deleción cromosómica más frecuente en humanos y se caracteriza por la tríada clínica que incluye cardiopatía congénita, hipocalcemia e inmunodeficiencia primaria. El 85-90% de los pacientes tienen microdeleciones en el cromosoma 22q11.2. Tomando como punto cardinal la cardiopatía congénita, se diseñó una estrategia para tamización y diagnóstico de SD22q11 con énfasis en la evaluación inmune. Es imprescindible realizar una historia clínica detallada y, posteriormente, un análisis cuantitativo y funcional de las subpoblaciones de linfocitos en sangre periférica para clasificarlo en SD22q11 completo (<1%) o parcial (95-99%) e instaurar las pautas de tratamiento en aspectos como: aislamiento del paciente, vacunación, profilaxis contra microorganismos oportunistas, uso de productos sanguíneos irradiados y reconstitución inmunológica. Sin embargo, el abordaje del paciente debe ser multidisciplinario para detectar y prevenir complicaciones a largo plazo que pueden ser graves, especialmente en los pacientes con SD22q11 completo.

In humans, 22q11 deletion syndrome (22q11DS) is considered the most common chromosome deletion syndrome. It is characterised by a clinical triad that includes congenital heart disease, hypocalcaemia and primary immunodeficiency. Approximately 85-90% of patients with this syndrome exhibit microdeletions in chromosome 22q11.2. Using congenital heart disease as a starting point, we designed a strategy for the screening and diagnosis of 22q11DS with an emphasis on immunological evaluation. A detailed clinical history and the subsequent quantitative and functional analyses of the lymphocyte subpopulations in the peripheral blood is crucial to classify as complete (<1%) or partial (95-99%) the disease and to guide clinicians in terms of patient isolation, vaccination, prophylaxis for opportunistic infections, use of irradiated blood products and immunological reconstitution. However, multidisciplinary care is necessary to detect and prevent long-term complications that could be severe, particularly in cases of complete 22q11DS.

Caso de fractura de cúbito en niño con osteogénesis imperfecta, implicaciones anestésicas / A case of ulna fracture in a child with osteogenesis imperfecta, anesthetic implications

Introducción: la Osteogénesis Imperfecta (OI) es una rara enfermedad congénita autosómica dominante del tejido conectivo con una incidencia aproximada de 1:21 000 a 1:60 000 nacimientos, con mayor incidencia en mujeres.1 Aunque también se han descrito casos de herencia recesiva o mutación espontánea.2 La Osteogénesis Imperfecta puede ser causada por la mutación en los cromosomas 7 o 17, en uno de los dos genes que codifcan el colágeno tipo 1A1 o 1A2. 3 Sus manifestaciones clínicas incluyen la susceptibilidad a las fracturas óseas y retraso del crecimiento, así como compromiso del tejido conectivo de otros órganos. Bajo este contexto existen múltiples implicaciones anestésicas que determinan un buen desenlace en el posoperatorio. Caso: es una revisión de caso clínico y revisión bibliográfca. Resultados: el presente caso muestra el manejo anestésico en un niño de 12 años con Osteogénesis Imperfecta, sometido a osteosíntesis por fractura de miembro superior. Patología poco frecuente en nuestro medio. Conclusiones: se puede concluir que el manejo anestésico de un paciente con Osteogénesis Imperfecta implica varios ámbitos desde su fragilidad ósea, vía aérea difícil, control de temperatura entre otros. Además que se requiere un abordaje multidisciplinario en el perioperatorio.

Introduction: Osteogenesis Imperfecta (OI) is a rare autosomal dominant congenital connective tissue disorder with an incidence of 1:21 000 to 1:60 000 births, with higher incidence in women. 1 Also we can fnd cases of recessive heritage or spontaneous 1 mutation. 2 Osteogenesis Imperfecta (OI), can be caused by mutations in chromosomes 7 or 17, in one of two genes encoding collagen type 1A1 or 1A2. 3 Its clinical manifestations include susceptibility to bone fractures and delayed growth and commitment of the connective tissue of other organs. In this context there are multiple anesthetic implications that determine a good postoperative outcome. Case: this is a clinical case review and a literature review. Results: this case shows de anesthetic management in a 12 years old boy with Osteogénesis Imperfecta, who underwent an osteosinthesis of an upper limb fracture. A rare pathology in our environment. Conclusions: we can conclude that the anesthetic management of a patient with Osteogénesis Imperfecta, involves several scopes from bone fragility, diffcult airway, core temperature control, etc. Besides that a multidisciplinary approach is required in the perioperative.