Pathogenic Variants in ACTRT1 Cause Acephalic Spermatozoa Syndrome

Yanwei Sha; Wensheng Liu; Lin Li; Mario Serafimovski; Vladimir Isachenko; Youzhu Li; Jing Chen; Bangrong Zhao; Yifeng Wang; Xiaoli Wei

doi:10.3389/fcell.2021.676246

Pathogenic Variants in ACTRT1 Cause Acephalic Spermatozoa Syndrome

Front Cell Dev Biol. 2021 Aug 6:9:676246. doi: 10.3389/fcell.2021.676246. eCollection 2021.

Authors

Yanwei Sha¹, Wensheng Liu^{2

3}, Lin Li⁴, Mario Serafimovski⁵, Vladimir Isachenko³, Youzhu Li⁶, Jing Chen⁶, Bangrong Zhao⁷, Yifeng Wang², Xiaoli Wei⁸

Affiliations

¹ Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen, China.
² Obstetrics and Gynecology Center, Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
³ Research Group for Reproductive Medicine, Department of Obstetrics and Gynecology, Medical Faculty, University of Cologne, Cologne, Germany.
⁴ Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
⁵ Center for Physiology and Pathophysiology, Medical Faculty, University of Cologne, Cologne, Germany.
⁶ Reproductive Medicine Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
⁷ NHC Key Laboratory of Family Planning and Healthy/Key Laboratory of Reproductive Medicine of Hebei Provincial, Shijiazhuang, China.
⁸ State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.

Abstract

Acephalic spermatozoa syndrome is a rare type of teratozoospermia, but its pathogenesis is largely unknown. Here, we performed whole-exome sequencing for 34 patients with acephalic spermatozoa syndrome and identified pathogenic variants in the X-linked gene, ACTRT1, in two patients. Sanger sequencing confirmed the pathogenic variants of ACTRT1 in the patients. Both pathogenic variants of ACTRT1 were highly conserved, and in silico analysis revealed that they were deleterious and rare. Actrt1-knockout mice exhibited a similar acephalic spermatozoa phenotype. Therefore, we speculated that mutations in ACTRT1 account for acephalic spermatozoa syndrome. Moreover, the patients in this study conceived their children through artificial insemination. This study provides further insights for clinicians and researchers regarding the genetic etiology and therapeutic strategies for acephalic spermatozoa patients with pathogenic variants in ACTRT1.

Keywords: ACTRT1; acephalic spermatozoa syndrome; pathogenic variants; teratozoospermia; whole-exome sequencing.