期刊
COLD SPRING HARBOR MOLECULAR CASE STUDIES
卷 8, 期 7, 页码 -出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/mcs.a006248
关键词
abdominal situs inversus
资金
- Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia [UID/Multi/04462/2013]
- Fundo Europeu de Desenvolvimento Regional(FEDER)
The majority of heterotaxy cases do not have a molecular diagnosis, but it is known that pathogenic variants in more than 50 genes can cause this condition. In this study, two unrelated individuals with heterotaxy syndrome were found to have biallelic loss-of-function variants in the DAND5 gene. Experimental results showed that these variants resulted in the inability of DAND5 to inhibit nodal signaling. This study reinforces the genetic and functional evidence for the role of DAND5 gene in causing heterotaxy syndrome.
The majority of heterotaxy cases do not obtain a molecular diagnosis, although pathogenic variants in more than 50 genes are known to cause heterotaxy. A heterozygous missense variant in DAND5, a nodal inhibitor, which functions in early development for establishment of right-left patterning, has been implicated in heterotaxy. Recently, the first case was reported of a DAND5 biallelic loss-of-function (LoF) variant in an individual with heterotaxy. Here, we describe a second unrelated individual with heterotaxy syndrome and a homozygous frameshift variant in DAND5 (NM_152654.2:c.197del [p.Leu66ArgfsTer22]). Using an in vitro assay, we demonstrate that the DAND5 c.197del variant is unable to inhibit nodal signaling when compared with the wild-type expression construct. This work strengthens the genetic and functional evidence for biallelic LoF variants in DAND5 causing an autosomal recessive heterotaxy syndrome.
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