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

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 / laterality defect / congenital heart disease / sperm defect / β-actin / SPAG6

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Acknowledgements

The study was supported by the National Natural Science Foundation of China (No. 81970268), the Natural Science Foundation of Hunan Province (No. 2023JJ30781), and the Graduate Student Scientific Research Innovation Project of Hunan Province (No. CX20220315).

Compliance with ethics guidelines

Conflicts of interest Zhuangzhuang Yuan, Xin Zhu, Xiaohui Xie, Chenyu Wang, Heng Gu, Junlin Yang, Liangliang Fan, Rong Xiang, Yifeng Yang, and Zhiping Tan declare no conflict of interest.

The study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University, and the study was performed in accordance with the ethical standards stated in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all patients included in the study.

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