Identification of a novel MYO1D variant associated with laterality defects,congenital heart diseases,and sperm defects in humans  

作　　者：Zhuangzhuang Yuan Xin Zhu Xiaohui Xie Chenyu Wang Heng Gu Junlin Yang Liangliang Fan Rong Xiang Yifeng Yang Zhiping Tan 

机构地区：[1]Department of Cardiovascular Surgery,The Second Xiangya Hospital of Central South University,Changsha,410011,China [2]Clinical Center for Gene Diagnosis and Therapy,The Second Xiangya Hospital of Central South University,Changsha,410011,China [3]Department of Cell Biology,School of Life Sciences,Central South University,Changsha,410013,China [4]Department of Gynecology and Obstetrics,Xiangya Hospital of Central South University,Changsha,410008,China

出　　处：《Frontiers of Medicine》2024年第3期558-564,共7页医学前沿（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81970268);the Natural Science Foundation of Hunan Province(No.2023JJ30781);the Graduate Student Scientific Research Innovation Project of Hunan Province(No.CX20220315).

摘　　要：The establishment of left–right asymmetry is a fundamental process in animal development.Interference with this process leads to a range of disorders collectively known as laterality defects,which manifest as abnormal arrangements of visceral organs.Among patients with laterality defects,congenital heart diseases(CHD)are prevalent.Through multiple model organisms,extant research has established that myosin-Id(MYO1D)deficiency causes laterality defects.This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D(NM_015194:c.1531G>A;p.D511N)in a consanguineous family with complex CHD and laterality defects.Further examination of the proband revealed asthenoteratozoospermia and shortened sperm.Afterward,the effects of the D511N variant and another known MYO1D variant(NM_015194:c.2293C>T;p.P765S)were assessed.The assessment showed that both enhance the interaction withβ-actin and SPAG6.Overall,this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans.Furthermore,this research established a connection between sperm defects and MYO1D variants.It offers guidance for exploring infertility and reproductive health concerns.The findings provide a critical basis for advancing personalized medicine and genetic counseling.

关 键 词：MYO1D laterality defect congenital heart disease sperm defect Β-ACTIN SPAG6 

分 类 号：R541[医药卫生—心血管疾病]