Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nucleic Acids Res ; 51(D1): D942-D949, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36420896

RESUMO

GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.


Assuntos
Biologia Computacional , Genoma Humano , Humanos , Animais , Camundongos , Anotação de Sequência Molecular , Biologia Computacional/métodos , Genoma Humano/genética , Transcriptoma/genética , Perfilação da Expressão Gênica , Bases de Dados Genéticas
2.
Brain ; 146(8): 3513-3527, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36917474

RESUMO

RNA polymerase I transcribes ribosomal DNA to produce precursor 47S rRNA. Post-transcriptional processing of this rRNA generates mature 28S, 18S and 5.8S rRNAs, which form the ribosomes, together with 5S rRNA, assembly factors and ribosomal proteins. We previously reported a homozygous variant in the catalytic subunit of RNA polymerase I, POLR1A, in two brothers with leukodystrophy and progressive course. However, the disease mechanism remained unknown. In this report, we describe another missense variant POLR1A NM_015425.3:c.1925C>A; p.(Thr642Asn) in homozygosity in two unrelated patients. Patient 1 was a 16-year-old male and Patient 2 was a 2-year-old female. Both patients manifested neurological deficits, with brain MRIs showing hypomyelinating leukodystrophy and cerebellar atrophy; and in Patient 1 additionally with hypointensity of globi pallidi and small volume of the basal ganglia. Patient 1 had progressive disease course, leading to death at the age of 16.5 years. Extensive in vitro experiments in fibroblasts from Patient 1 documented that the mutated POLR1A led to aberrant rRNA processing and degradation, and abnormal nucleolar homeostasis. Proteomics data analyses and further in vitro experiments documented abnormal protein homeostasis, and endoplasmic reticulum stress responses. We confirm that POLR1A biallelic variants cause neurodegenerative disease, expand the knowledge of the clinical phenotype of the disorder, and provide evidence for possible pathological mechanisms leading to POLR1A-related leukodystrophy.


Assuntos
Doenças Neurodegenerativas , RNA Polimerase I , Masculino , Feminino , Humanos , RNA Polimerase I/genética , RNA Polimerase I/metabolismo , Doenças Neurodegenerativas/genética , Proteostase , RNA Ribossômico/metabolismo , Ribossomos , Processamento Pós-Transcricional do RNA
3.
Brain ; 145(7): 2602-2616, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35104841

RESUMO

Bi-allelic pathogenic variants in ZBTB11 have been associated with intellectual developmental disorder, autosomal recessive 69 (MRT69; OMIM 618383). We report five patients from three families with novel, bi-allelic variants in ZBTB11. We have expanded the clinical phenotype of MRT69, documenting varied severity of atrophy affecting different brain regions and described combined malonic and methylmalonic aciduria as a biochemical manifestation. As ZBTB11 encodes for a transcriptional regulator, we performeded chromatin immunoprecipitation-sequencing targeting ZBTB11 in fibroblasts from patients and controls. Chromatin immunoprecipitation-sequencing revealed binding of wild-type ZBTB11 to promoters in 238 genes, among which genes encoding proteins involved in mitochondrial functions and RNA processing are over-represented. Mutated ZBTB11 showed reduced binding to 61 of the targeted genes, indicating that the variants act as loss of function. Most of these genes are related to mitochondrial functions. Transcriptome analysis of the patient fibroblasts revealed dysregulation of mitochondrial functions. In addition, we uncovered that reduced binding of the mutated ZBTB11 to ACSF3 leads to decreased ACSF3 transcript level, explaining combined malonic and methylmalonic aciduria. Collectively, these results expand the clinical spectrum of ZBTB11-related neurological disease and give insight into the pathophysiology in which the dysfunctional ZBTB11 affect mitochondrial functions and RNA processing contributing to the neurological and biochemical phenotypes.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Erros Inatos do Metabolismo , Malformações do Sistema Nervoso , Erros Inatos do Metabolismo dos Aminoácidos/genética , Encéfalo , Humanos , Erros Inatos do Metabolismo/genética
4.
Am J Hum Genet ; 105(6): 1112-1125, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31708117

RESUMO

Huntington disease (HD) is a fatal neurodegenerative disorder caused by a gain-of-function mutation in HTT. Suppression of mutant HTT has emerged as a leading therapeutic strategy for HD, with allele-selective approaches targeting HTT SNPs now in clinical trials. Haplotypes associated with the HD mutation (A1, A2, A3a) represent panels of allele-specific gene silencing targets for efficient treatment of individuals with HD of Northern European and indigenous South American ancestry. Here we extend comprehensive haplotype analysis of the HD mutation to key populations of Southern European, South Asian, Middle Eastern, and admixed African ancestry. In each of these populations, the HD mutation occurs predominantly on the A2 HTT haplotype. Analysis of HD haplotypes across all affected population groups enables rational selection of candidate target SNPs for development of allele-selective gene silencing therapeutics worldwide. Targeting SNPs on the A1 and A2 haplotypes in parallel is essential to achieve treatment of the most HD-affected subjects in populations where HD is most prevalent. Current allele-specific approaches will leave a majority of individuals with HD untreated in populations where the HD mutation occurs most frequently on the A2 haplotype. We further demonstrate preclinical development of potent and selective ASOs targeting SNPs on the A2 HTT haplotype, representing an allele-specific treatment strategy for these individuals. On the basis of comprehensive haplotype analysis, we show the maximum proportion of HD-affected subjects that may be treated with three or four allele targets in different populations worldwide, informing current allele-specific HTT silencing strategies.


Assuntos
Etnicidade/genética , Inativação Gênica , Haplótipos , Proteína Huntingtina/antagonistas & inibidores , Doença de Huntington/terapia , Mutação , Oligonucleotídeos Antissenso/uso terapêutico , Alelos , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Expansão das Repetições de Trinucleotídeos
5.
Hum Mutat ; 41(12): 2179-2194, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33131181

RESUMO

Ciliopathies are clinically and genetically heterogeneous diseases. We studied three patients from two independent families presenting with features of Joubert syndrome: abnormal breathing pattern during infancy, developmental delay/intellectual disability, cerebellar ataxia, molar tooth sign on magnetic resonance imaging scans, and polydactyly. We identified biallelic loss-of-function (LOF) variants in CBY1, segregating with the clinical features of Joubert syndrome in the families. CBY1 localizes to the distal end of the mother centriole, contributing to the formation and function of cilia. In accordance with the clinical and mutational findings in the affected individuals, we demonstrated that depletion of Cby1 in zebrafish causes ciliopathy-related phenotypes. Levels of CBY1 transcript were found reduced in the patients compared with controls, suggesting degradation of the mutated transcript through nonsense-mediated messenger RNA decay. Accordingly, we could detect CBY1 protein in fibroblasts from controls, but not from patients by immunofluorescence. Furthermore, we observed reduced ability to ciliate, increased ciliary length, and reduced levels of the ciliary proteins AHI1 and ARL13B in patient fibroblasts. Our data show that CBY1 LOF-variants cause a ciliopathy with features of Joubert syndrome.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Transporte/genética , Cerebelo/anormalidades , Ciliopatias/genética , Anormalidades do Olho/genética , Doenças Renais Císticas/genética , Mutação/genética , Proteínas Nucleares/genética , Retina/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Adolescente , Animais , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Criança , Pré-Escolar , Cílios/metabolismo , Cílios/patologia , Ciliopatias/diagnóstico por imagem , Ciliopatias/patologia , Anormalidades do Olho/diagnóstico por imagem , Anormalidades do Olho/patologia , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Homozigoto , Humanos , Lactente , Recém-Nascido , Doenças Renais Císticas/diagnóstico por imagem , Doenças Renais Císticas/patologia , Imageamento por Ressonância Magnética , Masculino , Linhagem , Fenótipo , Retina/diagnóstico por imagem , Retina/patologia , Receptor Smoothened/metabolismo , Adulto Jovem , Peixe-Zebra/genética
6.
BMC Med Genet ; 21(1): 96, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381069

RESUMO

BACKGROUND: Joubert syndrome (JBTS) is a genetically heterogeneous group of neurodevelopmental syndromes caused by primary cilia dysfunction. Usually the neurological presentation starts with abnormal neonatal breathing followed by muscular hypotonia, psychomotor delay, and cerebellar ataxia. Cerebral MRI shows mid- and hindbrain anomalies including the molar tooth sign. We report a male patient with atypical presentation of Joubert syndrome type 23, thus expanding the phenotype. CASE PRESENTATION: Clinical features were consistent with JBTS already from infancy, yet the syndrome was not suspected before cerebral MRI later in childhood showed the characteristic molar tooth sign and ectopic neurohypophysis. From age 11 years seizures developed and after few years became increasingly difficult to treat, also related to inadequate compliance to therapy. He died at 23 years of sudden unexpected death in epilepsy (SUDEP). The genetic diagnosis remained elusive for many years, despite extensive genetic testing. We reached the genetic diagnosis by performing whole genome sequencing of the family trio and analyzing the data with the combination of one analysis pipeline for single nucleotide variants (SNVs)/indels and one for structural variants (SVs). This lead to the identification of the most common variant detected in patients with JBTS23 (OMIM# 616490), rs534542684, in compound heterozygosity with a 8.3 kb deletion in KIAA0586, not previously reported. CONCLUSIONS: We describe for the first time ectopic neurohypophysis and SUDEP in JBTS23, expanding the phenotype of this condition and raising the attention on the possible severity of the epilepsy in this disease. We also highlight the diagnostic power of WGS, which efficiently detects SNVs/indels and in addition allows the identification of SVs.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ciclo Celular/genética , Cerebelo/anormalidades , Morte Súbita/patologia , Epilepsia/genética , Anormalidades do Olho/genética , Doenças Renais Císticas/genética , Retina/anormalidades , Anormalidades Múltiplas/mortalidade , Anormalidades Múltiplas/patologia , Adulto , Cerebelo/patologia , Criança , Morte Súbita/epidemiologia , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/mortalidade , Deficiências do Desenvolvimento/patologia , Epilepsia/mortalidade , Epilepsia/patologia , Anormalidades do Olho/mortalidade , Anormalidades do Olho/patologia , Feminino , Heterozigoto , Humanos , Mutação INDEL , Doenças Renais Císticas/mortalidade , Doenças Renais Císticas/patologia , Masculino , Neuro-Hipófise/metabolismo , Neuro-Hipófise/patologia , Retina/patologia , Sequenciamento Completo do Genoma , Adulto Jovem
7.
J Stroke Cerebrovasc Dis ; 25(1): 102-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26522268

RESUMO

BACKGROUND: Thrombophilia is an enhanced tendency of arterial or venous blood clot formation. The frequently assessed hereditary thrombophilia mutations associated with stroke are methylenetetrahydrofolate reductase (MTHFR) c.677C>T, Factor V (F5) c.1691G>A (Leiden), and prothrombin (F2) c.20210G>A. The aim of this study was to describe the prevalence of the 3 mutations in ischemic stroke patients in Sri Lanka. METHODS: A database of clinical details and genetic test results of stroke patients referred for thrombophilia screening from June 2006 to April 2014 was maintained prospectively and analyzed retrospectively. RESULTS: A total of 400 ischemic stroke patients (319 arterial, 66 venous, and 15 location unreported) were screened for hereditary thrombophilia. Patients with the MTHFR c.677C>T, F5 c.1691G>A, and F2 c.20210G>A mutations were 17.3%, 3.3%, and .5% of the total cohort, respectively. F5 mutation was present in a statistically significant number of patients with venous thrombosis (P = .005) compared to patients with arterial thrombosis. The MTFHR and F2 mutations showed no such significant association. The mean age of patients with MTHFR, F5, and F2 mutations was 29 (±15), 34 (±11), and 38 (±5.6) years, respectively. CONCLUSION: MTHFR c.677C>T is the predominant mutation and the only mutation that had patients with the homozygous mutant genotype. Venous thrombosis showed a significant association with the F5 c.1691G>A mutation.


Assuntos
Resistência à Proteína C Ativada/genética , Isquemia Encefálica/etiologia , Fator V/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Protrombina/genética , Trombofilia/genética , Resistência à Proteína C Ativada/epidemiologia , Adolescente , Adulto , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/genética , Criança , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , Regiões Promotoras Genéticas/genética , Estudos Retrospectivos , Fatores de Risco , Sri Lanka/epidemiologia , Trombofilia/epidemiologia , Adulto Jovem
8.
J Obstet Gynaecol Res ; 41(4): 596-600, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25331108

RESUMO

AIM: The use of prophylactic antibiotics for laparoscopy of uncomplicated gynecologic conditions is controversial. The aim of this study was to assess whether prophylactic antibiotics is necessary to prevent early postoperative infections and febrile morbidity in elective laparoscopic surgery for benign gynecologic conditions. MATERIAL AND METHODS: A total of 218 patients who underwent laparoscopy for uncomplicated gynecologic conditions were recruited into the study over a 1-year period. Following recruitment into the study, they were divided into two groups (ratio 1:1). Patients were divided into either group A (n = 115) the therapy arm or group B (n = 103) the placebo arm. Group A patients received oral azithromycin 1 g daily for 3 days (i.e. the day before, the day of and the day after the procedure) while group B received placebo therapy. Post-procedural febrile and infection morbidity was analyzed. RESULTS: Morbidity was absent in 91.3% of patients in both groups A and B. The primary outcome measure of postoperative fever was present in eight patients from each group. The secondary outcome measure of postoperative infection was present in one patient from the group that did not receive prophylaxis (group B), who had a surgical site infection. There were no patients with urinary tract infection or pelvic inflammatory disease during the study. CONCLUSION: Antibiotics prophylaxis was not able to achieve statistically significant reduction in postoperative febrile or infective morbidity in laparoscopic gynecologic surgery for benign uncomplicated conditions.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Azitromicina/uso terapêutico , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Laparoscopia/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Sri Lanka , Infecção da Ferida Cirúrgica/etiologia , Adulto Jovem
9.
Dev World Bioeth ; 15(3): 226-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25280225

RESUMO

INTRODUCTION: Stored human samples and the establishment of biobanks are increasing in the world. Along with this there are the questions of ethics that arise such as the correct method of obtaining informed consent for research on stored samples and the policies involved in collaborative research using collected samples. This study is an attempt to evaluate the researchers, academics and policy makers' views on these ethical aspects. METHODS: This was an anonymised study involving a Sri Lankan population of researchers, ethics committee members, and policy makers. A self administered questionnaire was utilised as the study instrument. The questionnaire captured four major areas of interest: demographic characteristics of respondents, their attitudes on informed consent policy, their opinion on rights of collaborating researchers, their attitudes on dealing with international differences in regulatory frameworks. RESULTS: The study included 55 responders with 40/55 (73%) agreeing that donors should receive the option of giving informed consent for future research, with 31/55 (56%) considering multiple- type consent options most appropriate. Regarding the issue of shared samples in collaborative research majority agreed that source country ethics review committee approval was necessary 53/55 (96%). CONCLUSION: The study concludes that sample donors should be given the option of giving advance consent to unspecified future research provided that future research is approved by an ethics committee. In collaborative research, it is necessary to involve ethics committees from donor countries in the research approval process.


Assuntos
Pessoal Administrativo/psicologia , Atitude , Bancos de Espécimes Biológicos/ética , Pesquisa Biomédica/ética , Pesquisadores/psicologia , Adulto , Feminino , Humanos , Consentimento Livre e Esclarecido , Masculino , Pessoa de Meia-Idade , Sri Lanka , Inquéritos e Questionários
10.
BMC Neurol ; 13: 191, 2013 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-24314096

RESUMO

BACKGROUND: Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka. METHODS: Data of 35 consecutive patients tested from 2007 to 2012 at the Human Genetics Unit, Faculty of Medicine, University of Colombo was analyzed retrospectively. Clinical data and genetic diagnostic results were reviewed. Statistical analysis was performed using descriptive statistics. RESULTS: Thirty patients had fully penetrant (FP) CAG repeat mutations and 5 had reduced penetrant (RP) CAG repeat mutations. In the FP group mean ages of onset and diagnosis were 37.5 and 40.4 years, while in the RP group it was 63.0 and 64.8 years respectively. The age of diagnosis ranged from 15 to 72 years, with 2 patients with Juvenile onset (<20 years) and 3 with late onset (>60 years) Huntington disease. The symptoms at diagnosis were predominantly motor (32/35 -91%). Three patients had psychiatric and behavioral disorders. The age difference between onset and genetic diagnosis showed significant delay in females compared to males (p < 0.05). Twenty two (62.8%) had a positive family history, with 13/22 (59.1%) showing a paternal inheritance of the disease. In both groups, those with a family history had a significantly lower age of presentation (p < 0.05). The mean CAG repeat length in patients with FP alleles was 44.6 ± 5 and RP alleles was 37.2 ± 1.1. Age of onset and CAG repeat length of the HTT gene showed significant inverse correlation (p < 0.0005, R2 = 0.727). CONCLUSIONS: The clinical and genetic features seen in patients with Huntington disease in the Sri Lankan study population were similar to that previously reported in literature.


Assuntos
Doença de Huntington/diagnóstico , Doença de Huntington/genética , Proteínas do Tecido Nervoso/genética , Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Idade de Início , Feminino , Frequência do Gene , Genótipo , Humanos , Proteína Huntingtina , Doença de Huntington/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Sri Lanka/epidemiologia , Adulto Jovem
11.
BMC Neurol ; 13: 39, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23634774

RESUMO

BACKGROUND: Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. METHODS: Thirty four patients with autosomal dominant ataxia were recruited. For every patient the following was done: recording of clinical details and genotyping for SCA 1, 2, 3, 6, 7, 8, 12, and 17. RESULTS: Sixty one per cent of the subjects were identified as SCA1. One subject had SCA2, 12 remain unidentified. Mean age at onset was 34.8 ± 10years for SCA1 and 32.7 ± 9.8 for non SCA1. 76% of SCA1 patients and 50% of non SCA1 were using walking aids. Quantification of symptoms and signs were similar in the SCA1 and non SCA1 groups. Clinical depression was evidenced in 68.4% of SCA1 and 75% non SCA-1 patients. Mean CAG repeat length in SCA1 patients was 52.0 ± 3.8, with greater anticipation seen with paternal inheritance. CONCLUSION: SCA1 was the predominant subtype and showed similar phenotype to previous reports. However, disease severity was higher and depression more prevalent in this population than previously described.


Assuntos
Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Adulto , Ataxina-1 , Ataxinas , Expansão das Repetições de DNA/genética , Saúde da Família , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sri Lanka/epidemiologia
12.
BMC Res Notes ; 8: 506, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26419729

RESUMO

BACKGROUND: Potocki-Lupski syndrome is a microduplication syndrome associated with duplication at 17p11.2. Features include facial dysmorphism, moderate to mild cognitive impairment and behavioural abnormalities including autism spectrum disorders. CASE PRESENTATION: We describe a patient from Sri Lanka that was referred for genetic assessment at 4 years of age due to subtle facial dysmorphism and expressive language impairment. She was diagnosed with Potocki-Lupski syndrome through multiplex ligation probe amplification. She carried two duplications; one in 17p11.2 consistent with Potocki-Lupski, and one in Xq including the region for X-linked intellectual disability. CONCLUSION: Despite the absence of expected behavioural symptoms, many features of this patient are in accordance with Potocki-Lupski syndrome. This is the first diagnosed patient in Sri Lanka.


Assuntos
Transtornos Cromossômicos/genética , Duplicação Cromossômica/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos X/genética , Anormalidades Múltiplas/genética , Pré-Escolar , Feminino , Humanos , Reação em Cadeia da Polimerase
15.
J Clin Res Pediatr Endocrinol ; 4(4): 223-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23032147

RESUMO

49,XXXXY is a rare sex chromosome polysomy with an incidence of 1 in 85 000 male births. It has a characteristic triad of mental retardation, skeletal malformation and hypogonadism. This is the first case report of a child with 49,XXXXY syndrome and renal agenesis. This child was referred for genetic testing at 14 years of age due to facial dysmorphism and hypergonadotropic hypogonadism. He had coarse facial features, cryptorchidism of the right testis, genu valgus deformities, and patent ductus arteriosus which are known associations of 49,XXXXY syndrome. He also had agenesis of the right kidney, hydronephrosis of the left kidney with hydroureter which is not a known association of 49,XXXXY syndrome. The patient was the offspring of a mother with gestational diabetes. There is a strong correlation between maternal diabetes and congenital anomalies, especially renal and cardiovascular anomalies. Additionally, it has been noted that gestational diabetes increases the incidence of chromosomal aneuploidies. The teratogenic effects of maternal diabetes during embryogenesis may be the causative factor for the final phenotype of 49,XXXXY syndrome and renal agenesis.


Assuntos
Diabetes Gestacional/fisiopatologia , Nefropatias/congênito , Síndrome de Klinefelter/complicações , Anormalidades Múltiplas/etiologia , Adolescente , Anormalidades Congênitas/etiologia , Anormalidades Congênitas/fisiopatologia , Anormalidades Craniofaciais , Fácies , Feminino , Humanos , Hipogonadismo/complicações , Hipogonadismo/etiologia , Rim/anormalidades , Rim/fisiopatologia , Nefropatias/complicações , Nefropatias/etiologia , Nefropatias/fisiopatologia , Síndrome de Klinefelter/etiologia , Síndrome de Klinefelter/fisiopatologia , Masculino , Atrofia Muscular/complicações , Atrofia Muscular/etiologia , Gravidez
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA