期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 32, 期 1, 页码 223-228出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2020040478
关键词
renal agenesis; gene expression; genetics and development
A study identified the causal role of GFRA1 gene variants in bilateral renal agenesis, potentially manifesting as an autosomal recessive, nonsyndromic form. This finding will facilitate early genetic diagnosis and improved genetic counseling for families at risk of BRA.
Background Congenital anomalies of the kidney and urinary tract (CAKUT) are one of the most common malformations identified in the fetal stage. Bilateral renal agenesis (BRA) represents the most severe and fatal form of CAKUT. Only three genes have been confirmed to have a causal role in humans (ITGA8, GREB1L, and FGF20). Methods Genome sequencing within a diagnostic setting and combined data repository analysis identified a novel gene. Results Two patients presented with BRA, detected during the prenatal period, without additional recognizable malformations. They had parental consanguinity and similarly affected, deceased siblings, suggesting autosomal recessive inheritance. Evaluation of homozygous regions in patient 1 identified a novel, nonsense variant inGFRA1 (NM_001348097.1:c.676C.T, p.[Arg226*]). We identified184 patients inour repository with renal agenesis and analyzed their exome/genome data. Of these 184 samples, 36 were from patients who presented with isolated renal agenesis. Two of them had loss-of-function variants in GFRA1. The second patient was homozygous for a frameshift variant (NM_001348097.1:c.1294delA, p.[Thr432Profs*13]). The GFRA1 gene encodes a receptor on the Wolffian duct that regulates ureteric bud outgrowth in the development of a functional renal system, and has a putative role in the pathogenesis of Hirschsprung disease. Conclusions These findings strongly support the causal role of GFRA1-inactivating variants for an autosomal recessive, nonsyndromic form of BRA. This knowledge will enable early genetic diagnosis and better genetic counseling for families with BRA.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据