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 abnorma...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.展开更多
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).
文摘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.
