RESUMO
WWOX has been recently implicated in autosomal recessive spinocerebellar ataxia type 12 (SCAR12) and severe early-onset epileptic encephalopathy (EOEE). By array comparative genomic hybridization, we identified a 0.6 Mb homozygous deletion in 16q23.1 in a fetus presenting with brain anomalies. His older sister who died at the age of 22 months from an EOEE was also homozygous for the copy number variations in 16q23.1. This deletion includes the first six exons of WWOX and results in a null genotype in homozygous patients. This family gives additional support for the implication of WWOX in severe EOEEs. We report for the first time prenatal ultrasound findings in a fetus with a WWOX-null genotype. Our study expands the range of brain abnormalities in WWOX-related EOEEs. This additional family confirms the genotype-phenotype correlation with WWOX-null alleles associated with the most severe form of WWOX-related epileptic encephalopathy with premature death.
Assuntos
Encefalopatias/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Oxirredutases/genética , Proteínas Supressoras de Tumor/genética , Encefalopatias/genética , Hibridização Genômica Comparativa , Epilepsia/genética , Evolução Fatal , Feminino , Genes Recessivos , Estudos de Associação Genética , Humanos , Recém-Nascido , Masculino , Gravidez , Ultrassonografia Pré-Natal , Oxidorredutase com Domínios WWRESUMO
OBJECTIVE: Alveolar capillary dysplasia (ACD) is one of the causes of pulmonary hypertension. Its diagnosis is histological but new pathogenetic data have emerged. The aim of this study was to describe a French cohort of patients with ACD to improve the comprehension and the diagnosis of this pathology which is probably underdiagnosed. METHODS: A retrospective observational study was conducted in French hospitals. Patients born between 2005 and 2017, whose biological samples were sent to the French genetic reference centres, were included. Clinical, histological and genetic data were retrospectively collected. RESULTS: We presented a series of 21 patients. The mean of postmenstrual age at birth was 37.6 weeks. The first symptoms appeared on the median of 2.5 hours. Pulmonary hypertension was diagnosed in 20 patients out of 21. Two cases had prolonged survival (3.3 and 14 months). Histological analysis was done on lung tissue from autopsy (57.1% of cases) or from percutaneous biopsy (28.6%). FOXF1 was found abnormal in 15 patients (71.4%): 8 deletions and 7 point mutations. Two deletions were found by chromosomal microarray. CONCLUSION: This study is one of the largest clinically described series in literature. It seems crucial to integrate genetics early into diagnostic support. We propose a diagnostic algorithm for helping medical teams to improve diagnosis of this pathology.
Assuntos
Fatores de Transcrição Forkhead/genética , Pulmão/patologia , Síndrome da Persistência do Padrão de Circulação Fetal , Alvéolos Pulmonares/anormalidades , Feminino , Humanos , Recém-Nascido , Masculino , Mutação , Síndrome da Persistência do Padrão de Circulação Fetal/genética , Síndrome da Persistência do Padrão de Circulação Fetal/patologia , Alvéolos Pulmonares/patologia , Estudos RetrospectivosRESUMO
Apert syndrome in monozygotic twins can lead to different phenotypic expression of the disease in the two fetuses. Apert syndrome can be associated with congenital left diaphragmatic hernia and cleft palate.