Identification of DNAH17 Variants in Han-Chinese Patients With Left-Right Asymmetry Disorders

Xuehui Yu; Lamei Yuan; Sheng Deng; Hong Xia; Xiaolong Tu; Xiong Deng; Xiangjun Huang; Xiao Cao; Hao Deng

doi:10.3389/fgene.2022.862292

Identification of DNAH17 Variants in Han-Chinese Patients With Left-Right Asymmetry Disorders

Front Genet. 2022 May 27:13:862292. doi: 10.3389/fgene.2022.862292. eCollection 2022.

Authors

Xuehui Yu^{1

2}, Lamei Yuan^{1

2

3

4}, Sheng Deng⁵, Hong Xia⁶, Xiaolong Tu⁶, Xiong Deng², Xiangjun Huang⁷, Xiao Cao², Hao Deng^{1

2

3

4}

Affiliations

¹ Health Management Center, The Third Xiangya Hospital, Central South University, Changsha, China.
² Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
³ Disease Genome Research Center, Central South University, Changsha, China.
⁴ Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
⁶ Department of Emergency, The Third Xiangya Hospital, Central South University, Changsha, China.
⁷ Department of General Surgery, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China.

Abstract

The formation of left-right asymmetry of the visceral organs is a conserved feature of the human body, and the asymmetry specification of structure and function is precisely orchestrated by multiple regulatory mechanisms. The abnormal results of organ positioning situs arise from defective cilia structure or function during embryogenesis in humans. In this study, we recruited two unrelated Han-Chinese families with left-right asymmetry disorders. The combination of whole-exome sequencing and Sanger sequencing identified two compound heterozygous variants: c.4109C>T and c.9776C>T, and c.612C>G and c.8764C>T in the dynein axonemal heavy chain 17 gene (DNAH17) in two probands with left-right asymmetry disorders. We report for the first time a possible association between DNAH17 gene variants and left-right asymmetry disorders, which is known as a causal gene for asthenozoospermia. Altogether, the findings of our study may enlarge the DNAH17 gene variant spectrum in human left-right asymmetry disorders, pave a way to illustrate the potential pathogenesis of ciliary/flagellar disorders, and provide supplementary explanation for genetic counseling.

Keywords: DNAH17; ciliary/flagellar disorders; gene variants; left–right asymmetry disorders; whole-exome sequencing.