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

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

doi:10.1007/s11684-023-1042-6

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

Front Med. 2024 Apr 30. doi: 10.1007/s11684-023-1042-6. Online ahead of print.

Authors

Zhuangzhuang Yuan^#^{1

2

3}, Xin Zhu^#⁴, Xiaohui Xie^{1

2}, Chenyu Wang³, Heng Gu^{1

2}, Junlin Yang^{1

2}, Liangliang Fan³, Rong Xiang³, Yifeng Yang¹, Zhiping Tan^{5

6}

Affiliations

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.
⁵ Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China. zhipingtan@csu.edu.cn.
⁶ Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South University, Changsha, 410011, China. zhipingtan@csu.edu.cn.

^# Contributed equally.

PMID: 38684630
DOI: 10.1007/s11684-023-1042-6

Abstract

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 with β-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.

Keywords: MYO1D; SPAG6; congenital heart disease; laterality defect; sperm defect; β-actin.