Next-generation sequencing profiling of miRNAs in individuals with 22q11.2 deletion syndrome revealed altered expression of miR-185-5p.

BACKGROUND: The 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with highly variable phenotypic manifestations, even though most patients present the typical 3 Mb microdeletion, usually affecting the same ~ 106 genes. One of the genes affected by this deletion is DGCR8, which plays a crucial role in miRNA biogenesis. Therefore, the haploinsufficiency of DGCR8 due to this microdeletion can alter the modulation of the expression of several miRNAs involved in a range of biological processes. RESULTS: In this study, we used next-generation sequencing to evaluate the miRNAs profiles in the peripheral blood of 12 individuals with typical 22q11DS compared to 12 healthy matched controls. We used the DESeq2 package for differential gene expression analysis and the DIANA-miTED dataset to verify the expression of differentially expressed miRNAs in other tissues. We used miRWalk to predict the target genes of differentially expressed miRNAs. Here, we described two differentially expressed miRNAs in patients compared to controls: hsa-miR-1304-3p, located outside the 22q11.2 region, upregulated in patients, and hsa-miR-185-5p, located in the 22q11.2 region, which showed downregulation. Expression of miR-185-5p is observed in tissues frequently affected in patients with 22q11DS, and previous studies have reported its downregulation in individuals with 22q11DS. hsa-miR-1304-3p has low expression in blood and, thus, needs more validation, though using a sensitive technology allowed us to identify differences in expression between patients and controls. CONCLUSIONS: Thus, lower expression of miR-185-5p can be related to the 22q11.2 deletion and DGCR8 haploinsufficiency, leading to phenotypic consequences in 22q11.2DS patients, while higher expression of hsa-miR-1304-3p might be related to individual genomic variances due to the heterogeneous background of the Brazilian population.

Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with a broad and heterogeneous phenotype, even though most of the deletions present similar sizes, involving ∼3 Mb of DNA. In a relatively large population of a Brazilian 22q11.2DS cohort (60 patients), we investigated genetic variants that could act as genetic modifiers and contribute to the phenotypic heterogeneity, using a targeted NGS (Next Generation Sequencing) with a specific Ion AmpliSeq panel to sequence nine candidate genes (CRKL, MAPK1, HIRA, TANGO2, PI4KA, HDAC1, ZDHHC8, ZFPM2, and JAM3), mapped in and outside the 22q11.2 hemizygous deleted region. In silico prediction was performed, and the whole-genome sequencing annotation analysis package (WGSA) was used to predict the possible pathogenic effect of single nucleotide variants (SNVs). For the in silico prediction of the indels, we used the genomic variants filtered by a deep learning model in NGS (GARFIELD-NGS). We identified six variants, 4 SNVs and 2 indels, in MAPK1, JAM3, and ZFPM2 genes with possibly synergistic deleterious effects in the context of the 22q11.2 deletion. Our results provide the opportunity for the discovery of the co-occurrence of genetic variants with 22q11.2 deletions, which may influence the patients´ phenotype.

Variants in KMT2A in Three Individuals with Previous Suspicion of 22q11.2 Deletion Syndrome.

The condition known as 22q11.2 deletion syndrome (MIM #188400) is a rare disease with a highly variable clinical presentation including more than 180 features; specific guidelines for screening individuals have been used to support clinical suspicion before confirmatory tests by Brazil's Craniofacial Project. Of the 2568 patients listed in the Brazilian Database on Craniofacial Anomalies, 43 individuals negative for the 22q11.2 deletion syndrome were further investigated through whole-exome sequencing. Three patients (6.7%) presented with heterozygous pathogenic variants in the KMT2A gene, including a novel variant (c.6158+1del) and two that had been previously reported (c.173dup and c.3241C>T); reverse phenotyping concluded that all three patients presented features of Wiedemann-Steiner syndrome, such as neurodevelopmental disorders and dysmorphic facial features (n = 3), hyperactivity and anxiety (n = 2), thick eyebrows and lower-limb hypertrichosis (n = 2), congenital heart disease (n = 1), short stature (n = 1), and velopharyngeal insufficiency (n = 2). Overlapping features between 22q11.2 deletion syndrome and Wiedemann-Steiner syndrome comprised neuropsychiatric disorders and dysmorphic characteristics involving the eyes and nose region; velopharyngeal insufficiency was seen in two patients and is an unreported finding in WDSTS. Therefore, we suggest that both conditions should be included in each other's differential diagnoses.

Neuropsychological Profile of 25 Brazilian Patients with 22q11.2 Deletion Syndrome: Effects of Clinical and Socioeconomic Variables.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with a heterogeneous neurocognitive phenotype, which includes psychiatric disorders. However, few studies have investigated the influence of socioeconomic variables on intellectual variability. The aim of this study was to investigate the cognitive profile of 25 patients, aged 7 to 32 years, with a typical ≈3 Mb 22q11.2 deletion, considering intellectual, adaptive, and neuropsychological functioning. Univariate linear regression analysis explored the influence of socioeconomic variables on intellectual quotient (IQ) and global adaptive behavior. Associations with relevant clinical conditions such as seizures, recurrent infections, and heart diseases were also considered. Results showed IQ scores ranging from 42 to 104. Communication, executive functions, attention, and visuoconstructive skills were the most impaired in the sample. The study found effects of access to quality education, family socioeconomic status (SES), and caregiver education level on IQ. Conversely, age at diagnosis and language delay were associated with outcomes in adaptive behavior. This characterization may be useful for better understanding the influence of social-environmental factors on the development of patients with 22q11.2 deletion syndrome, as well as for intervention processes aimed at improving their quality of life.

GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases.

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.

X-Chromosome Dependent Differences in the Neuronal Molecular Signatures and Their Implications in Sleep Patterns.

Biological factors and mechanisms that drive sex differences observed in sleep disturbances are understudied and poorly understood. The extent to which sex chromosome constitution impacts on sex differences in circadian patterns is still a knowledge void in the sleep medicine field. Here we focus on the neurological consequences of X-chromosome functional imbalances between males and females and how this molecular inequality might affect sex divergencies on sleep. In light of the X-chromosome inactivation mechanism in females and its implications in gene regulation, we describe sleep-related neuronal circuits and brain regions impacted by sex-biased modulations of the transcriptome and the epigenome. Benefited from recent large-scale genetic studies on the interplay between X-chromosome and brain function, we list clinically relevant genes that might play a role in sex differences in neuronal pathways. Those molecular signatures are put into the context of sleep and sleep-associated neurological phenotypes, aiming to identify biological mechanisms that link X-chromosome gene regulation to sex-biased human traits. These findings are a significant step forward in understanding how X-linked genes manifest in sleep-associated transcriptional networks and point to future research opportunities to address female-specific clinical manifestations and therapeutic responses.

Intellectual performance profi le of a sample of children and adolescents from Brazil with 22q11. 2 Deletion Syndrome (22q11. 2DS) based on the Wechsler Scale / Perfil de desempenho intelectual de uma amostra brasileira de crianças e adolescentes com Síndrome da Deleção 22q11. 2 (22q11. 2DS)com base na Escala Wechsler

The 22q11.2 Deletion Syndrome (22q11.2DS), the most common human chromosome microdeletion syndrome, is associated with a very heterogeneous neurocognitive phenotype. One of the main characteristics of the syndrome spectrum is the intellectual variability, which encompasses average performance and intellectual disability and discrepancies between Verbal Intelligence Quotient and Performance Verbal Intelligence Quotient, with greater impairment in nonverbal tasks. The present study aimed at investigating the intellectual performance aspects of a 21children and adolescents sample from Brazil who had been diagnosed with 22q11.2DS, based on the Wechsler Intelligence Scale for Children - 4th edition. The samples were reviewed considering the differences between indices. The results revealed an Full Scale Intelligence Quotient predominant in the borderline range (42 to 104) and a significant discrepancy between the indices of Verbal Comprehension and Perceptual Reasoning in 42% of the sample. With regard to the performance in the subtests alone, a better performance was found in Similarities, whereas block design, matrix reasoning, digit span and letter-number sequencing subtests were the most challenging. These findings indicate that a comprehensive assessment of intellectual performance aspects covering the different measures of the Wechsler Intelligence Scale may contribute to a broader understanding of the neurocognitive phenotype associated with 22q11.2DS.

A Síndrome da Deleção 22q11.2 (SD22q11.2), microdeleção cromossômica mais frequente em humanos, é associada a um fenótipo neurocognitivo muito heterogêneo. Uma das principais características do espectro da síndrome é a variabilidade intelectual, que abrange de desempenho médio a deficiência intelectual, bem como discrepâncias entre Quociente de Inteligência Verbal e de Quociente de Inteligência de Execução, com maior prejuízo nas tarefas não verbais. O presente estudo teve por objetivo investigar aspectos do desempenho intelectual de uma amostra brasileira de 21 crianças e adolescentes diagnosticados com SD22q11.2, com base nos indicadores da Wechsler Intelligence Scale for Children - 4th edition. As amostras foram analisadas considerando diferenças entre os índices. Os resultados revelaram predomínio de Quociente de Inteligência Total na faixa limítrofe, entre 42 e 104, assim como discrepância significativa entre os índices de compreensão verbal e organização perceptual em 42% da amostra. No que concerne ao desempenho nos subtestes de forma isolada, um melhor resultado foi verificado em semelhanças, ao passo que cubos, raciocínio matricial, dígitos e sequência de números e letras foram os mais desafiadores. Esses achados indicam que uma avaliação abrangente de aspectos do desempenho intelectual contemplando as diversas medidas da Escala Wechsler de Inteligência pode contribuir para uma compreensão mais ampla do fenótipo neurocognitivo associado à SD22q11.2.

Cytogenomic assessment of the diagnosis of 93 patients with developmental delay and multiple congenital abnormalities: The Brazilian experience

OBJECTIVE: The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients. METHODS: We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes. CONCLUSION: The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis.

Interrupção do arco aórtico tipo B em uma paciente com síndrome de olho de gato / Interrupted aortic arch type B in A patient with cat eye syndrome / Interrupción del arco aórtico tipo B en una paciente con síndrome del ojo de gato

Relatamos um caso de paciente com Síndrome do Olho de Gato (Cat Eye Syndrome-CES) e interrupção do arco aórtico tipo B, um achado típico na síndrome da deleção 22q11.2. A análise cromossômica e a técnica de hibridização fluorescente in situ (FISH) mostraram um cromossomo marcador isodicêntrico supranumerário com bi-satélite derivado do cromossomo 22. O segmento de 22pter a 22q11.2 no cromossomo supranumerário encontrado em nosso paciente não estava em sobreposição com a região deletada em pacientes com a síndrome da deleção 22q11.2. Entretanto, o achado de interrupção do arco aórtico tipo B não é usual na CES, mas é um defeito cardíaco freqüente na síndrome da deleção 22q11.

We report a patient with cat eye syndrome and interrupted aortic arch type B, a typical finding in the 22q11.2 deletion syndrome. Chromosomal analysis and fluorescent in situ hybridization (FISH) showed a supernumerary bisatellited isodicentric marker chromosome derived from chromosome 22. The segment from 22pter to 22q11.2 in the supernumerary chromosome found in our patient does not overlap with the region deleted in patients with the 22q11.2 deletion syndrome. However, the finding of an interrupted aortic arch type B is unusual in CES, although it is a frequent heart defect in the 22q11 deletion syndrome.

Informamos un caso de paciente con Síndrome de Ojo de Gato (Cat Eye Syndrome-CES) e Interrupción del Arco Aórtico tipo B, un hallazgo típico en el síndrome de la deleción 22q11.2. El análisis cromosómico y la técnica de hibridación in situ fluorescente (FISH) mostraron un cromosoma marcador isodicéntrico supernumerario bisatelitado derivado del cromosoma 22. El segmento de 22pter a 22q11.2 en el cromosoma supernumerario encontrado en nuestro paciente no estaba en sobreposición con la región deletada en pacientes con el síndrome de la deleción 22q11.2. Con todo, el hallazgo de interrupción del arco aórtico tipo B no es usual en el CES, sino que es un defecto cardíaco frecuente en el síndrome de deleción 22q11.

Deleção 22q11.2 em pacientes com defeito cardíaco conotruncal e fenótipo da síndrome da deleção 22q11.2 / Deleción 22q11.2 en pacientes con defecto cardiaco conotruncal y fenotipo del síndrome de la deleción 22q11.2 / 22q11.2 deletion in patients with conotruncal heart defect and del22q syndrome phenotype

FUNDAMENTO: A síndrome da deleção 22q11.2 é a mais freqüente síndrome de microdeleção humana. O fenótipo é altamente variável e caracterizado por defeito cardíaco conotruncal, dismorfias faciais, insuficiência velofaríngea, dificuldade de aprendizagem e retardo mental. OBJETIVO: O objetivo deste trabalho foi investigar a freqüência da deleção 22q11.2 em uma amostra brasileira de indivíduos portadores de cardiopatia conontrucal isolada e do fenótipo da síndrome da deleção 22q11.2. MÉTODOS: Vinte e nove pacientes foram estudados por meio de citogenética clássica, por hibridação in situ fluorescente (FISH) e por técnicas moleculares. RESULTADOS: A análise citogenética por meio de bandamento G revelou cariótipo normal em todos os pacientes, com exceção de um que apresentou cariótipo 47,XX,+idic(22)(q11.2). Com o uso de técnicas moleculares, a deleção foi observada em 25 por cento dos pacientes, todos portadores do fenótipo da síndrome da deleção 22q11.2. Em nenhum dos casos, a deleção foi herdada dos pais. A freqüência da deleção 22q11.2 foi maior no grupo de pacientes portadores do espectro clínico da síndrome da deleção 22q11.2 do que no grupo de pacientes com cardiopatia conotruncal isolada. CONCLUSÃO: A investigação da presença da deleção e sua correlação com os dados clínicos dos pacientes podem auxiliar os pacientes e suas famílias a terem um melhor aconselhamento genético e um seguimento clínico mais adequado.

BACKGROUND: The 22q11.2 deletion syndrome is the most frequent human microdeletion syndrome. The phenotype is highly variable, being characterized by conotruncal heart defect, facial dysmorphisms, velopharyngeal insufficiency, learning difficulties and mental retardation. OBJECTIVE: The objective of this study was to investigate the frequency of deletion 22q11.2 in a Brazilian sample of individuals with isolated conotruncal heart defect and 22q11.2 deletion syndrome phenotype. METHODS: Twenty-nine patients were studied by classical cytogenetics, by fluorescence in situ hybridization (FISH), and by molecular techniques. RESULTS: Cytogenetic analysis by G-banding revealed a normal karyotype in all patients except one who presented a 47,XX,+idic(22)(q11.2) karyotype. Using molecular techniques, a deletion was observed in 25 percent of the patients, all exhibiting a 22q11.2 deletion syndrome phenotype. In none of the cases the deletion was inherited from the parents. The frequency of 22q11.2 deletion was higher in patients with the clinical spectrum of the 22q11.2 deletion syndrome than in patients with isolated conotruncal heart defect. CONCLUSION: Investigating the presence of the deletion and its correlation with the patients' clinical data can help the patients and their families to have a better genetic counseling and more adequate clinical follow-up.

FUNDAMENTO: El síndrome de la deleción 22q11.2 es el más frecuente síndrome de microdeleción humana. El fenotipo, altamente variable, se caracteriza por defecto cardiaco conotruncal, dismorfias faciales, insuficiencia velofaríngea, dificultad de aprendizaje y retardo mental. OBJETIVO: El objetivo de este trabajo fue investigar la frecuencia tanto de la deleción 22q11.2 en una muestra brasileña de individuos portadores de cardiopatía conotrucal aislada, como del fenotipo del síndrome de la delación 22q11.2. MÉTODOS: Se estudiaron a 29 pacientes por medio de citogenética clásica, por hibridación in situ fluorescente (FISH) y también por técnicas moleculares. RESULTADOS: El análisis citogenético por medio de bandeo G reveló cariotipo normal en todos los pacientes, con excepción de uno, que presentó cariotipo 47,XX,+idic(22)(q11.2). Con la utilización de técnicas moleculares, se observó la deleción en el 25 por ciento de los pacientes, todos portadores del fenotipo del síndrome de la deleción 22q11.2. En ningún de los casos, la deleción se heredó de los padres. La frecuencia de la deleción 22q11.2 en el grupo de pacientes portadores del espectro clínico de este síndrome resultó mayor que en el grupo de pacientes con cardiopatía conotruncal aislada. CONCLUSIÓN: La investigación de la presencia de deleción y su correlación con los datos clínicos de los pacientes pueden auxiliar los pacientes y sus familias a tener un mejor aconsejamiento genético, así como un seguimiento clínico más adecuado.

Clinical checklists in the selection of mentally retarded males for molecular screening of fragile X syndrome

Fragile X syndrome is the most frequent cause of inherited mental retardation. The phenotype in this syndrome is quite variable and less conspicuous in younger patients, making clinical diagnosis difficult and thus making molecular diagnosis necessary. The use of clinical checklists in mentally retarded individuals can help selecting patients to be given priority in the molecular investigation for the fragile-X mutation in the FMR1 gene. We evaluated two clinical checklists in a sample of 200 Brazilian male patients with mental retardation. The highest scores in the two checklists concentrated among the 19 males (9.5 percent) found to carry full mutations. Our results confirm the importance of fragile-X checklists as a clinical tool in the study of mentally retarded patients.

Cytogenetic study of women with premature ovarian failure

A etiologia da insuficiência ovariana prematura (POF) ainda é desconhecida na maioria dos pacientes. Uma vez que alguns casos estäo associados a anormalidades do cromossomo X, estudamos citogeneticamente pacientes portadores de POF. Comparamos as culturas de linfócitos de onze pacientes com as de indivíduos controle de mesmas idades. Todos os indivíduos estudados apresentaram cariótipos normais. As freqüências de células aneuplóides e com aberraçöes cromossômicas estruturais näo diferiram entre os grupos. Verificamos uma maior freqüência de aneuploidia e de divisäo prematura do centrômero do cromossomo X nos dois grupos.

Síndrome de tremor e ataxia associada ao X frágil: rastreamento por PCR em amostra de idosos / Fragile X-associated tremor/ataxia syndrome: PCR-based screening in a sample of elderly men

Introdução: A presença de sequências repetidas de DNA já foi identificada como marcadoras de certas doenças neuropsiquiátricas. O gene FMR1 possui sequência rica em repetições CGG, sujeito a expansão quando transmitido por via materna. Alelos pré-mutados (55200 repetições CGG). Na mutação completa, o gene é inativado determinando a síndrome do X frágil (FRAX). Os portadores da pré-mutação não apresentam deficiência cognitiva associada à FRAX, porém, um subgrupo desses indivíduos com mais de 50 anos de idade desenvolve uma síndrome neurológica progressiva, a síndrome de tremor/ataxia associada ao X frágil (Fragile X-associated Tremor/Ataxia Syndrome–FXTAS). Objetivos: Este estudo investigou as características clínicas e moleculares dos familiares de quatro homens com mais de 50 anos de idade, familiares de indivíduos FRAX, uma vez que esses indivíduos possuem risco elevado de desenvolver o quadro de FXTAS. Resultados: Nenhum dos pacientes avaliados possuía FXTAS. Conclusão: A síndrome FXTAS foi recentemente descrita e é pouco conhecida no meio clínico e científico. Dessa forma, a avaliação de familiares de indivíduos FRAX pode contribuir para o melhor entendimento da doença e permitir a determinação de sua incidência na população brasileira.

Introduction: The presence of repeated sequences was already identified as markers of neuropsychiatric diseases. The FMR1 gene shelters a CGGrich sequence which is vulnerable to expansion when transmitted through maternal lineage. Premutated alleles (55 200 CGG repeats). In the full mutation range, the gene is inactivated causing the fragile X syndrome (FRAX). Premutation carriers do not present mental retardation, however a subgroup of permutation carriers older than 50 years can develop a progressive neurological syndrome, the Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). Objectives: This approach had investigated clinical and molecular features offour males - relatives of FRAX individuals – due to the high risk of developing FXTAS. Results: None of the investigated patients had FXTAS. Conclusion: This syndrome was recently described and there is little knowledge about it by clinicians and scientists. Thus, evaluation of people in this condition can contribute to the better understanding of the disease and its incidence in the Brazilian population.

Sister chromatid exchange in mutagenicity testing: a study of mercapto oxazolyl carboxylic acid

As trocas entre cromátides irmäs (TCI) e o ciclo celular foram estudados por meio da técnica BrdU-Giemsa para avaliar a sua capacidade e sensibilidade de detecçäo de efeitos tóxicos, particularmente os mutagênicos e/ou carcinogênicos. Foi utilizada uma substância clastogênica - o ácido mercapto oxazolil carboxílico, uma droga anti-reumática - para avaliar seu efeito "in vitro" quanto a induçäo de (TCI), aberraçöes cromossômicas e quanto ao ciclo celular. Foi verificado que esta droga induziu um aumento na freqüência de (TCI) em concentraçöes inferiores àquelas que produziram um aumento na freqüência de aberraçöes cromossômicas. A droga, nas concentraçöes mais baixas utilizadas, provocou uma antecipaçäo do ciclo celular enquanto que na concentraçäo mais elevada produziu um atraso deste. Assim, a avaliaçäo das (TCI) e do ciclo celular configura-se como um método potente e sensível no estudo da mutagenicidade e toxicidade de drogas

A modified R-abanding technique

No presente trabalho descrevemos uma modificaçäo da técnica de baneamento R, que utiliza incorporaçäo de 5-BrdU, tratamento pelo Hoechst 33258 e coloraçäo pelo Giemsa (RBG). Esta técnica produz boa qualidade de bandamento além de alta reprodutibilidade

Deletion 9p and duplication 17p due to a translocation t(9; 17)(p23; p13)pat

Relatamos o caso de um paciente apresentando monossomia 9p e trissomia 17p parciais decorrentes de uma translocaçäo equilibrada paterna t(9;17)(p23;p13). O fenótipo resultante no paciente assemelha-se mais ao observado na síndrome da monossomia 9p.

Satellite association and nucleolar organizer regions in the elderly

A expressäo dos genes ribossômicos representada pelas freqüências de associaçöes de satélites e de regiöes organizadoras de nucléolo (RONs) ativas foi avaliada em culturas de linfócitos de um grupo de recém-nascidos e um grupo de indivíduos com idades entre 70-90 anos, através de técnica de coloraçäo pela prata. Observamos freqüências semelhantes de RONs ativas em ambos os grupos ao lado de uma freqüência mais elevada de associaçöes de satélites no grupo dos idosos