RESUMO
BACKGROUND AND AIM: APO CII, one of several cofactors which regulate lipoprotein lipase enzyme activity, plays an essential role in lipid metabolism. Deficiency of APO CII is an ultra-rare autosomal recessive cause of familial chylomicronemia syndrome. We present the long-term clinical outcomes of 12 children with APO CII deficiency. METHODS AND RESULTS: The data of children with genetically confirmed APO CII deficiency were evaluated retrospectively. Twelve children (8 females) with a mean follow-up of 10.1 years (±3.9) were included. At diagnosis, the median age was 60 days (13 days-10 years). Initial clinical findings included lipemic serum (41.6%), abdominal pain (41.6%), and vomiting (16.6%). At presentation, the median triglyceride (TG) value was 4341 mg/dL (range 1277-14,110). All patients were treated with a restricted fat diet, medium-chain triglyceride (MCT), and omega-3-fatty acids. In addition, seven patients (58.3%) received fibrate. Fibrate was discontinued in two patients due to rhabdomyolysis and in one patient because of cholelithiasis. Seven (58.3%) patients experienced pancreatitis during the follow-up period. One female experienced recurrent pancreatitis and was treated with fresh frozen plasma (FFP). CONCLUSIONS: Apo CII deficiency is an ultra-rare autosomal recessive condition of hypertriglyceridemia associated with significant morbidity and mortality. Low-fat diet and MCT supplementation are the mainstays of therapy, while the benefit of TG-lowering agents are less well-defined.
Assuntos
Biomarcadores , Hipertrigliceridemia , Triglicerídeos , Humanos , Feminino , Masculino , Estudos Retrospectivos , Criança , Resultado do Tratamento , Triglicerídeos/sangue , Fatores de Tempo , Pré-Escolar , Lactente , Biomarcadores/sangue , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/terapia , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Recém-Nascido , Apolipoproteína C-II/genética , Apolipoproteína C-II/deficiência , Apolipoproteína C-II/sangue , Dieta com Restrição de Gorduras , Hipolipemiantes/uso terapêutico , Hiperlipoproteinemia Tipo I/diagnóstico , Hiperlipoproteinemia Tipo I/terapia , Hiperlipoproteinemia Tipo I/genética , Hiperlipoproteinemia Tipo I/sangue , Hiperlipoproteinemia Tipo I/complicações , Fenótipo , Fatores Etários , Ácidos Fíbricos/uso terapêutico , Predisposição Genética para Doença , Fatores de RiscoRESUMO
OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder and Sluggish Cognitive Tempo (SCT) might be a second inattention disorder that might be even affected by different attention pathways. SCT is characterized by daydreaming, mental confusion, staring blankly and hypoactivity. In the present study, we evaluated 5 common variants (rs6265, rs3746544, rs1051312, rs133946 and rs133945) located in 3 candidate genes (BDNF, SNAP25 and SYN III) that are known to take part in synaptic plasticity and neurotransmitter transmission. METHODS: We tested the effects of these variants on neuropsychological findings assessed by a computer-based neuropsychological test battery in children with inattention symptoms (SCT and/or ADHD). RESULTS: BDNF (rs6265), SNAP25 (rs3746544 and rs1051312) and SYN III (rs133946 and rs133945) polymorphisms were associated with variable cognitive measures. BDNF gene (rs6265) polymorphism Met allele carriers and SNAP25 gene (rs3746544) T allele carriers had an association with the attention domain. SNAP25 gene (rs1051312) C allele carriers were only associated with reaction time scores. Cognitive flexibility, which is one of the key components of executive function evaluation and shifting attention test scores were associated with BDNF (rs6265) Met allele and SYN III (rs133946) gene G allele. SYN III (rs133945) gene C allele carriers had an association with verbal memory correct hit scores. CONCLUSIONS: As a conclusion, BDNF, SNAP25 and SYN III genes were associated with specific neurocognitive outcomes in children with inattention symptoms. It is important to note that exploring genotyping effects on neurocognitive functions instead of a heterogeneous psychiatric diagnosis can improve our understanding of psychopathologies.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Fator Neurotrófico Derivado do Encéfalo , Função Executiva , Sinapsinas , Proteína 25 Associada a Sinaptossoma , Criança , Humanos , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Fator Neurotrófico Derivado do Encéfalo/genética , Cognição , Proteína 25 Associada a Sinaptossoma/genética , Sinapsinas/genéticaRESUMO
Background/aim: Although cutting edge procedures such as cell-free fetal DNA isolation from maternal blood are now available, invasive prenatal tests are still being used extensively for prenatal diagnosis. The study aims to evaluate the demographic data, indications, and cytogenetic results of 9297 results of patients who underwent prenatal invasive testing for genetic analysis that were referred for the last 20 years in a University Medical Genetics Center. Materials and methods: The records of 8363 amniocenteses, 626 chorionic villus, and 308 cordocenteses samples were retrospectively evaluated and analyzed regarding referral reasons, indications and their cytogenetic results. The total numbers and the percentages of each group were recorded; Chi-square and logistic regression analyses were performed to give the statistical likelihood of different events. Results: The number of referrals decreased significantly after 2009. Risk of having trisomy 21 as well as trisomy 13 and 18 significantly increased in parallel with advanced maternal age. When the 2125 age group was compared to the older age groups in terms of having a trisomy 21 pregnancy, the risk doubled in the 3640, 5 times higher in 4145 and 10-fold in 4650 age groups. No significant linear correlation between maternal serum screening test results and trisomy 21 was found, however the difference between the pregnancies whom cut-off value above and below 1/250 in maternal serum screening test were significant. Conclusion: These data have provided useful information on the frequency of referrals to the reference genetics department, and the feasibility of genetic services. By reviewing the indications and their corresponding results, we can offer invaluable insights that will be useful in genetic counseling and also in the development of more effective genetic strategies.
Assuntos
Aberrações Cromossômicas , Síndrome de Down , Aconselhamento Genético/métodos , Diagnóstico Pré-Natal/estatística & dados numéricos , Adulto , Aneuploidia , Feminino , Genética Médica , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Turquia/epidemiologia , UniversidadesRESUMO
Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by susceptibility to bacterial and fungal infections resulting from the inadequacy of phagocytic leucocytes to produce reactive oxygen radicals. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB (OMIM #300481) gene encoding the gp91(phox) protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA (OMIM #608508), NCF1 (OMIM #608512), NCF2 (OMIM #608515) and NCF4 (OMIM #601488) genes encoding p22(phox), p47(phox), p67(phox) and p40(phox), respectively. The genetic mutation of one of the cytosolic p47phox/p67phox proteins and membrane-bound gp91phox/p22phox proteins, which constitutes the NADPH oxidase enzyme complex, causes the disease. In this study, we evaluated the clinical, laboratory and genetic findings and the prognostic effects of molecular inheritance of our 24 CGD cases (14 XR, 10 autosomal recessive-AR). Consanguinity (three XR and all AR cases) showed statistically significant relationship with the type of hereditary inheritance (P < 0.001). 83% patients had an infection since early infancy. The mean age of initiation of symptoms was earlier in XR cases, and 78% patients had respiratory tract infections. Bone marrow transplantation was performed in five XR cases (two ex) and four AR (one ex) cases. Three of nine XR and two of six AR cases deceased on medical follow-up. In countries especially with high consanguinity rates, the early diagnosis for appropriate prophylactic treatment of CGD is quietly important to avoid from recurrent severe infections, early death and fatal complications of late transplantation.
Assuntos
Consanguinidade , Doença Granulomatosa Crônica/imunologia , NADPH Oxidases/metabolismo , Adolescente , Idade de Início , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Seguimentos , Genes Recessivos/genética , Genes Ligados ao Cromossomo X/genética , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Humanos , Masculino , Mutação/genética , NADPH Oxidase 2/genética , Espécies Reativas de Oxigênio/metabolismo , Estudos Retrospectivos , Resultado do Tratamento , Turquia/epidemiologiaRESUMO
Alström syndrome (ALMS) is an autosomal recessive disease characterized by multiple organ involvement, including neurosensory vision and hearing loss, childhood obesity, diabetes mellitus, cardiomyopathy, hypogonadism, and pulmonary, hepatic, renal failure and systemic fibrosis. Alström Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to have a role in microtubule organization, intraflagellar transport, endosome recycling and cell cycle regulation. Here, we report extensive phenotypic and genetic analysis of a large cohort of Turkish patients with ALMS. We evaluated 61 Turkish patients, including 11 previously reported, for both clinical spectrum and mutations in ALMS1. To reveal the molecular diagnosis of the patients, different approaches were used in combination, a cohort of patients were screened by the gene array to detect the common mutations in ALMS1 gene, then in patients having any of the common ALMS1 mutations were subjected to direct DNA sequencing or next-generation sequencing for the screening of mutations in all coding regions of the gene. In total, 20 distinct disease-causing nucleotide changes in ALMS1 have been identified, eight of which are novel, thereby increasing the reported ALMS1 mutations by 6% (8/120). Five disease-causing variants were identified in more than one kindred, but most of the alleles were unique to each single patient and identified only once (16/20). So far, 16 mutations identified were specific to the Turkish population, and four have also been reported in other ethnicities. In addition, 49 variants of uncertain pathogenicity were noted, and four of these were very rare and probably or likely deleterious according to in silico mutation prediction analyses. ALMS has a relatively high incidence in Turkey and the present study shows that the ALMS1 mutations are largely heterogeneous; thus, these data from a particular population may provide a unique source for the identification of additional mutations underlying Alström Syndrome and contribute to genotype-phenotype correlation studies.
Assuntos
Síndrome de Alstrom/genética , Consanguinidade , Estudos de Associação Genética , Adolescente , Síndrome de Alstrom/patologia , Proteínas de Ciclo Celular , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Mutação , Linhagem , Isoformas de Proteínas/genética , Proteínas/genética , TurquiaRESUMO
Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder characterized by the obstruction of venous channels in the brain. Genetic factors play a significant role in CVT development, and recent studies have identified gain-of-function mutations in coagulation factors, including factor IX (FIX). This case report focuses on a unique neonatal case of CVT, where an X-chromosome duplication involving the F9 gene resulted in increased FIX activity. The neonate presented with feeding difficulties, weight loss, nystagmus, and seizures. Imaging and laboratory tests confirmed a 554-kb X-chromosome duplication encompassing the F9 gene. This genetic abnormality likely contributed to the elevated FIX activity level and subsequent CVT development. Understanding the relationship between coagulation factor abnormalities and CVT risk expands our knowledge of thrombophilia's genetic basis and may aid in the development of targeted treatment strategies for CVT management.
Assuntos
Trombose Intracraniana , Trombofilia , Trombose Venosa , Recém-Nascido , Humanos , Fator IX/genética , Duplicação Gênica , Trombose Venosa/genética , Duplicação Cromossômica , Trombofilia/complicações , Trombofilia/diagnóstico , Trombofilia/genética , Trombose Intracraniana/genética , Fatores de RiscoRESUMO
Isolated deficiency of complex II is a rare inborn error of metabolism, accounting for approximately 2% of mitochondrial diseases. Mitochondrial complex II deficiency is predominantly seen in cases with bi-allelic SDHA mutations. To our knowledge, only 11 patients and five pathogenic variants have been reported for the SDHB gene. Our patient had a severe clinical presentation with seizures and sepsis, and died at the age of 2 months. Muscle biopsy analysis was compatible with mitochondrial myopathy with complex II deficiency. The family was given a molecular diagnosis for their child 2 years after his death via a clinical exome test of a frozen muscle biopsy specimen and a novel homozygous missense variant c.592 A>G (p.Ser198Gly) in SDHB gene was detected by next-generation sequencing. Here, we present another patient with a novel homozygous SDHB variant causing severe complex II deficiency and early death.
Assuntos
Complexo II de Transporte de Elétrons/deficiência , Erros Inatos do Metabolismo/genética , Doenças Mitocondriais/genética , Succinato Desidrogenase/genética , Consanguinidade , Complexo II de Transporte de Elétrons/genética , Evolução Fatal , Humanos , Recém-Nascido , MasculinoRESUMO
OBJECTIVES: Turner syndrome (TS) is one of the most common chromosomal abnormalities with an incidence of approximately one in 2,500 live births. Short stature and primary ovarian insufficiency are two most important characteristic findings of TS. Turner syndrome karyotypes include monosomy X, mosaic structure and X chromosome structural anomalies. Genotypic and phenotypic characteristics vary among cases. This study aimed to evaluate the clinical variations observed in TS cases with the copy number variations (CNV) detected by microarray study. METHODS: Fifty-three patients diagnosed with TS, between the ages of 0-18 were included in the study. Peripheral blood samples were taken from 36 cases for microarray study. RESULTS: Karyotypes were as follows: thirty-three of cases were 45,X, 7 were 45,X/46,XX, 6 were 45,X/46,Xi(Xq), 2 were 46,Xi(Xq), 2 were 45,X/46,r(X), 1 was 45,X/46,Xi(Xp), 1 was 45,X/46,XY and 1 was 45,X/46,X+mar(idicY) karyotype. A significant correlation was found between karyotype groups and FSH values of the cases (p=0.034). In monosomy X and mosaic isochromosome Xq cases, the FSH value was found to be significantly higher than those with 45,X/46,XX mosaic karyotype. CNVs were found in 8 (22.2%) out of 36 cases whose microarray study was performed. Unexpected atypical findings were discussed in the light of the characteristics of CNVs. CONCLUSIONS: In conclusion, the microarray method has a great contribution in explaining many unexpected findings in TS cases. Moreover, those CNV findings may contribute for the explanation of the underlying mechanisms of those anomalies.
Assuntos
Síndrome de Turner , Adolescente , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Hormônio Foliculoestimulante , Humanos , Lactente , Recém-Nascido , Cariótipo , Cariotipagem , Síndrome de Turner/diagnóstico , Síndrome de Turner/genéticaRESUMO
OBJECTIVE: Tetrasomy 9p is a rare fetal condition. Cases are usually mosaic. Here, we present a non-mosaic tetrasomy 9p case with cytogenetic analysis, fluorescence in situ hybridization, microarray data, ultrasound findings, and phenotypic presentation. CASE REPORT: A pregnancy was referred to cytogenetic analysis because of increased nuchal translucency in prenatal ultrasound at 13 weeks of gestation. Prenatal laboratory analysis revealed an extra marker chromosome with a non-mosaic pattern. Ultrasonographic findings were unilateral cleft lip and palate, micrognathia, and atrioventricular septal defect at the 17th week; additionally, ventriculomegaly, left axis deviation of the fetal heart, and a single umbilical artery were determined at the 23rd week. CONCLUSION: Phenotypic severity in non-mosaic tetrasomy 9p widely differs depending on the chromosomal content. We recommend performing appropriate genetic tests in those pregnancies with the suspicion of tetrasomy 9p, evaluating the mosaic state, and following those cases with detailed ultrasonographic examinations.
Assuntos
Cromossomos Humanos Par 9/genética , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Análise Citogenética/métodos , Diagnóstico Pré-Natal , Adulto , Amniocentese , Aneuploidia , Feminino , Aconselhamento Genético , Humanos , Hibridização in Situ Fluorescente , Análise em Microsséries , Mosaicismo , Medição da Translucência Nucal , Gravidez , UltrassonografiaRESUMO
BACKGROUND: Grade IV gliomas are classified as glioblastoma (GBM), which is the most malignant brain cancer type. Various genetic and epigenetic mechanisms play a role in the initiation and progression of GBM. MicroRNAs (miRNAs) are small, non-coding RNA molecules that belong to the main epigenetic regulatory RNA class that plays different roles in either physiological or pathological conditions, including GBM pathogenesis regulating expression levels of the target genes. Brain Cancer Stem Cells (BCSCs) are responsible for poor prognosis, including therapy resistance and relapse. Epigenetic regulation mediated by miRNAs is also a critical component of BCSC selfrenewal and differentiation properties. Propolis is a resinous substance collected by honey bees from various plant sources. The flavonoid content of propolis varies depending on the collection region and the extraction method. Although there are studies that include the effects of different originated-propolis on the miRNA expression levels of the glioblastoma cells, the impact on the BCSCs has not been studied yet. OBJECTIVE: This study aims to evaluate the effects of propolis obtained from Aydin, a city in western Turkey, on miRNA expression levels of BCSCs and GBM cells. METHODS: Aydin propolis was dissolved in 60% ethanol, and after evaporation, distilled water was added to prepare the propolis stock solution. The flavonoids content of the Aydin propolis was determined by MS Q-TOF analysis. Commercially obtained U87MG and BCSCs were used as in-vitro brain cancer models. Cytotoxic and apoptotic effects of Aydin propolis were determined via WST-1 assay and Annexin V test, respectively. The miRNA expression profile was investigated using the real-time qRT-PCR method. The fold changes were calculated by the2-ΔΔCt method. The miRNA-mRNA-pathway interactions, including significantly altered miRNAs, were determined using different bioinformatics tools and databases. RESULTS: Quercetin 3-methyl ether was the main component of the Aydin propolis. Aydin propolis did not show significant cytotoxic and apoptotic effects on both GBM and BCSCs up to 2mg/ml concentration. Aydin propolis treatment decreased the expression of nine miRNAs in the U87MG and five miRNAs in the BCSCs. Moreover, ten miRNAs have upregulated from 2.22 to 10.56 folds in propolis treated GBM cells compared to the control group significantly (p<0.05). In the study, the potential roles of two new miRNAs, whose regulations in glioma were not previously defined, were identified. One of them was miR-30d-5p, a novel potential oncomiR in GBM, which was 2.46 folds downregulated in Aydin propolis treated GBM cells. The other one is miR-335-5p, which is a potential tumor suppressor miR in GBM, that was 5.66 folds upregulated in Aydin propolis treated GBM cells. FOXO pathway, its upstream and downstream regulators, and critically neuronal developmental regulators, NOTCH and WNT pathways, were determined as the most deregulated pathways in Aydin propolis treated cells. CONCLUSION: The determination of the anti-cancer effect of Aydin propolis on the miRNA expression of GBM, especially on cancer stem cells, may contribute to the elucidation of brain cancer genetics by supporting further analyses.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , Extratos Vegetais/farmacologia , Própole/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Sedimentos Geológicos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Própole/química , Própole/isolamento & purificação , Relação Estrutura-Atividade , Células Tumorais Cultivadas , TurquiaRESUMO
A limited numbers of published studies evaluate the referral reasons for genetic counseling services in the literature. These studies are focused on prenatal genetic counseling services, in particular, prenatal diagnosis. In order to provide the most effective and helpful genetic counseling services, genetics professionals need adequate knowledge about the profile of individuals referred for these services. In addition, physicians need increased awareness of the nature of genetic issues in order to make appropriate referrals. This study was intended to provide a descriptive analysis of the referral reasons of patients that received genetic counseling at a genetics center in Izmir, Turkey during an 11-year period. A total of 8965 records generated between 1998 and 2008 from one genetic center (which consists of The Department of Medical Genetics and Division of Pediatric Genetics) were evaluated retrospectively. Of these, 6,258 involved referrals for prenatal reasons, and 2,707 involved referrals for postnatal reasons. Both prenatal and postnatal records were further classified into more specific categories of referral reasons. The most common reason for genetic counseling among the prenatal patients was advanced maternal age (42.0%), followed by high risk results on prenatal biochemical screening tests such as second trimester double test [(serum concentration of alphafetoprotein (AFP), beta-human chorionic gonadotropin (beta-HCG)], triple test (serum concentration of AFP, beta-HCG, oestriol) and integrated test (26.5%). The most common indications for postnatal patients were recurrent miscarriages (28.2%) and infertility (19.7%). A significant increase in number of specific categories of referrals for genetic counseling was observed for the last 3 years after the establishment of the Medical Genetics Department. These data provide useful information about the frequency of referrals to the genetics department, and the feasibility of genetic services. Organization of genetic services and systematic procedures for genetic counseling and genetic testing may improve the public's awareness of genetics and ensure a high standard of patient care.
Assuntos
Aconselhamento Genético , Encaminhamento e Consulta , Adulto , Humanos , Diagnóstico Pré-Natal , TurquiaRESUMO
Although the polymorphic heterochromatin regions of chromosomes (heteromorphisms) have been extensively studied for their phenotypic effects on humans, co-occurrences of chromosome 1, 9, 16 and Y heteromorphisms and of acrocentric variants have never been studied on humans with an objective scoring system. Here we compared the frequencies of individual heteromorphisms on a total of 602, 768 and 224 patients with the indications of infertility, recurrent miscarriage and in vitro fertilization (IVF) failure, respectively and on 272 controls. Then we examined whether there were significant co-occurrences between heteromorphisms within and between the groups. There were no statistically significant differences in the frequencies of heteromorphisms between the groups. Both statistically significant and non-significant correlations were observed within the non-acrocentric and certain acrocentric heteromorphisms in each group. When these co-occurrences were examined between the groups, a 2.2 fold increased risk of IVF failure in males in the presence of either chromosome 13 or chromosome 21 variants was observed (95 %CI:1.1-4.2). We conclude that the simultaneous manifestations of heteromorphisms have no effect on reproductive failure. There seems to be a correlation between the non-acrocentric heteromorphisms (1qh+, 9qh+, 16qh + and Yqh+/-), which might be the result of complex interactions of formation of these heterochromatin regions. The correlations observed between certain acrocentric chromosomes might be related to satellite association and nucleolus formation. The increased risk observed in males with IVF failure in the presence of either chromosome 13 or 21 variants should be interpreted cautiously due to the heterogeneity of the group.
Assuntos
Aborto Habitual/patologia , Heterocromatina/patologia , Infertilidade/patologia , Feminino , Humanos , Masculino , Polimorfismo Genético , Estudos RetrospectivosRESUMO
OBJECTIVE: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3'-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). METHODS: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. RESULTS: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. CONCLUSION: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Cognição , Feminino , Genótipo , Humanos , Repetições Minissatélites/genética , Receptores de Dopamina D4/genéticaRESUMO
When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals. For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment modality has to be decided for a particular patient regarding hematopoietic stem cell transplantation or intravenous immunoglobulin replacement therapy with P. jiroveci prophylaxis. A seven-year-old male patient was admitted with recurrent upper and lower respiratory tract infections and recurrent otitis media. His initial immunologic evaluation revealed low IgG and normal IgA and IgM levels with normal lymphocyte phenotyping and inadequate specific antibody responses. He was diagnosed as common variable immunodeficiency and began to receive intravenous immunoglobulin (IVIG) (0.5 gm/kg) with four-week intervals. During follow-up for 23 years under IVIG therapy, he was extremely well and never had severe infections. In 2017, targeted next generation sequencing was performed in order to understand his molecular pathology. A previously described hemizygous c.31C>T(p.Arg11Ter) mutation was found in CD40LG gene. The mother was heterozygous carrier for this mutation and his sister did not have any mutation. Flow cytometric analysis for CD40LG expression on activated T cells showed highly decreased, but not absent, CD40LG expression. In conclusion, diagnostic delay is a clinical problem for patients with CD40LG deficiency, because of low or normal IgM levels, showing that all the hypogammaglobulinemic patients, not only with high serum IgM levels, but also with normal to low IgM levels, have to be examined for CD40LG expression on activated T lymphocytes. Secondly, type of CD40LG mutations leads to enormous interpatient variations regarding serum IgM levels, CD40LG levels on activated T cells, age at diagnosis, severity of clinical findings, and follow-up therapies with or without hematopoietic stem cell therapy.
Assuntos
Assimetria Facial/genética , Esquizofrenia/genética , Trissomia/genética , Dissomia Uniparental/genética , Criança , Cromossomos Humanos Par 21/genética , Assimetria Facial/complicações , Feminino , Genoma , Humanos , Repetições de Microssatélites , Mosaicismo , Esquizofrenia/complicações , Trissomia/fisiopatologia , Dissomia Uniparental/fisiopatologiaRESUMO
Seckel syndrome is an autosomal recessive disease presenting with microcephalic dwarfism, mental retardation and facial and skeletal abnormalities. Morgagni hernia is quite rare, constituting 1-6% of all diaphragmatic hernias. It is asymptomatic, especially in childhood. Morgagni hernia has never been reported in patients with Seckel Syndrome. Here we report a 3-year-old boy diagnosed as having Seckel Syndrome with Morgagni hernia, which has to be considered during physical examination of patients.
Assuntos
Anormalidades Múltiplas/patologia , Hérnia Diafragmática/complicações , Pré-Escolar , Hérnia Diafragmática/diagnóstico por imagem , Humanos , Masculino , Radiografia , SíndromeRESUMO
Aarskog-Scott syndrome (ASS) is a rare X-linked recessive genetic disorder caused by FGD1 mutations. FGD1 regulates the actin cytoskeleton and regulates cell growth and differentiation by activating the c-Jun N-terminal kinase signaling cascade. ASS is characterized by craniofacial dysmorphism, short stature, interdigital webbing and shawl scrotum. However, there is a wide phenotypic heterogeneity because of the additional clinical features. ASS and some syndromes including the autosomal dominant inherited form of Robinow syndrome, Noonan syndrome, pseudohypoparathyroidism, Silver-Russel and SHORT syndrome have some overlapping phenotypic features. Herein, we report a patient with ASS and a large anterior fontanel who was initially diagnosed as Robinow syndrome. He was found to have a novel c.1340+2 T>A splice site mutation on the FGD1 gene.
Assuntos
Anormalidades Múltiplas/genética , Processamento Alternativo/genética , Fontanelas Cranianas/patologia , Anormalidades Craniofaciais/genética , Nanismo/genética , Face/anormalidades , Doenças Genéticas Ligadas ao Cromossomo X/genética , Genitália Masculina/anormalidades , Fatores de Troca do Nucleotídeo Guanina/genética , Deformidades Congênitas da Mão/genética , Cardiopatias Congênitas/genética , Deformidades Congênitas dos Membros/genética , Mutação/genética , Anormalidades Urogenitais/genética , Anormalidades Múltiplas/patologia , Anormalidades Craniofaciais/complicações , Anormalidades Craniofaciais/patologia , Nanismo/complicações , Nanismo/patologia , Face/patologia , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Genitália Masculina/patologia , Deformidades Congênitas da Mão/complicações , Deformidades Congênitas da Mão/patologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/patologia , Humanos , Recém-Nascido , Deformidades Congênitas dos Membros/complicações , Deformidades Congênitas dos Membros/patologia , Masculino , Prognóstico , Anormalidades Urogenitais/complicações , Anormalidades Urogenitais/patologiaRESUMO
Objective: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3′-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). Methods: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. Results: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. Conclusion: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.