尿道下裂
多重连接依赖探针扩增
遗传学
病因学
外显子组测序
生物
表型
大规模并行测序
队列
表观遗传学
基因
儿科
生物信息学
医学
内科学
DNA测序
外显子
作者
Barbara Leitao Braga,Nathália Lisboa Gomes,Mirian Yumie Nishi,Bruna L. Freire,Rafael Loch Batista,José Antônio Diniz Faria,Mariana F.A. Funari,Anna Benedetti,Amanda de Moraes Narcizo,Laís Cavalca Cardoso,Antônio Marcondes Lerário,Gil Guerra‐Júnior,Elaine Maria Frade Costa,Sorahia Domenice,Alexander A.L. Jorge,Berenice B. Mendonça
出处
期刊:Sexual Development
[S. Karger AG]
日期:2021-09-09
卷期号:16 (1): 27-33
被引量:6
摘要
Hypospadias is a common congenital disorder of male genital formation. Children born small for gestational age (SGA) present a high frequency of hypospadias of undetermined etiology. No previous study investigated the molecular etiology of hypospadias in boys born SGA using massively parallel sequencing. Our objective is to report the genetic findings of a cohort of patients born SGA with medium or proximal hypospadias. We identified 46 individuals with this phenotype from a large cohort of 46,XY DSD patients, including 5 individuals with syndromic features. DNA samples from subjects were studied by either whole exome sequencing or target gene panel approach. Three of the syndromic patients have 5 main clinical features of Silver-Russell syndrome (SRS) and were first studied by MLPA. Among the syndromic patients, loss of DNA methylation at the imprinting control region H19/IGF2 was identified in 2 individuals with SRS clinical diagnosis. Two novel pathogenic variants in compound heterozygous state were identified in the CUL7 gene establishing the diagnosis of 3M syndrome in one patient, and a novel homozygous variant in TRIM37 was identified in another boy with Mulibrey nanism phenotype. Among the non-syndromic subjects, 7 rare heterozygous variants were identified in 6 DSD-related genes. However, none of the variants found can explain the phenotype by themselves. In conclusion, a genetic defect that clarifies the etiology of hypospadias was not found in most of the non-syndromic SGA children, supporting the hypothesis that multifactorial causes, new genes, and/or unidentified epigenetic defects may have an influence in this condition.
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