RESUMO
BACKGROUND: Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder. These variants have been identified in a group of children with neurodevelopmental disorders with microcephaly, arthrogryposis, and structural brain anomalies. SMPD4 encodes a sphingomyelinase that hydrolyzes sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes. MATERIALS AND METHODS: For the efficient prenatal diagnosis of rare and undiagnosed diseases, the parallel detection of copy number variants (CNVs) and single nucleotide variants using whole-exome analysis is required. A physical examination of the parents was performed. Karyotype and whole-exome analysis were performed for the fetus and the parents. RESULTS: A fetus with microcephaly and arthrogryposis; biallelic null variants (c.387-1G>A; Chr2[GRCh38]: g.130142742_130202459del) were detected by whole-exome sequencing (WES). We have reported for the first time the biallelic loss-of-function mutations in SMPD4 in patients born to unrelated parents in China. CONCLUSION: WES could replace chromosomal microarray analysis and copy number variation sequencing as a more cost-effective genetic test for detecting CNVs and diagnosing highly heterogeneous conditions.
Assuntos
Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Microcefalia , Polimorfismo de Nucleotídeo Único , Diagnóstico Pré-Natal , Esfingomielina Fosfodiesterase , Humanos , Variações do Número de Cópias de DNA/genética , Sequenciamento do Exoma/métodos , Feminino , Diagnóstico Pré-Natal/métodos , Esfingomielina Fosfodiesterase/genética , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Microcefalia/genética , Heterozigoto , Artrogripose/genética , Artrogripose/diagnóstico , Masculino , Exoma/genética , Mutação/genética , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/diagnósticoRESUMO
The aortic short axis view demonstrated the widening of the pulmonary artery and the membrane-like echo in the pulmonary artery divided it into true lumen and false lumen. And the flow of the ruptured openings on the band-like echo was clearly revealed by Color Doppler.
