Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome PMID: 27640305

ADC Targets in Oncology

2026-04-10

Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome

Am J Hum Genet. 2016 Oct 6;99(4):942-949. doi: 10.1016/j.ajhg.2016.08.004.

Fuxi Zhu ¹ , Fengsong Wang ² , Xiaoyu Yang ³ , Jingjing Zhang ⁴ , Huan Wu ⁴ , Zhou Zhang ⁴ , Zhiguo Zhang ⁵ , Xiaojin He ⁵ , Ping Zhou ⁵ , Zhaolian Wei ⁵ , Jozef Gecz ⁶ , Yunxia Cao ⁷

Affiliations

1. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Institute of Reproductive Genetics, Anhui Medical University, Hefei 230022, China; School of Life Science, Anhui Medical University, Hefei 230022, China. Electronic address: [email protected].
2. School of Life Science, Anhui Medical University, Hefei 230022, China.
3. Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
4. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Institute of Reproductive Genetics, Anhui Medical University, Hefei 230022, China.
5. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Institute of Reproductive Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
6. School of Medicine, Robinson Research Institute, The University of Adelaide, and South Australian Health and Medical Research Institute, Adelaide, South Australia 5006, Australia.
7. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Institute of Reproductive Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. Electronic address: [email protected].

Abstract

Acephalic spermatozoa syndrome is a rare and severe form of teratozoospermia characterized by a predominance of headless spermatozoa in the ejaculate. Family clustering and consanguinity suggest a genetic origin; however, causative mutations have yet to be identified. We performed whole-exome Sequencing in two unrelated infertile men and subsequent variant filtering identified one homozygous (c.824C>T [p.Thr275Met]) and one compound heterozygous (c.1006C>T [p.Arg356Cys] and c.485T>A [p.Met162Lys]) SUN5 (also named TSARG4) variants. Sanger Sequencing of SUN5 in 15 additional unrelated infertile men revealed four compound heterozygous (c.381delA [p.Val128Serfs^∗7] and c.824C>T [p.Thr275Met]; c.381delA [p.Val128Serfs^∗7] and c.781G>A [p.Val261Met]; c.216G>A [p.Trp72^∗] and c.1043A>T [p.Asn348Ile]; c.425+1G>A/c.1043A>T [p.Asn348Ile]) and two homozygous (c.851C>G [p.Ser284^∗]; c.350G>A [p.Gly114Arg]) variants in six individuals. These 10 SUN5 variants were found in 8 of 17 unrelated men, explaining the genetic defect in 47.06% of the affected individuals in our cohort. These variants were absent in 100 fertile population-matched control individuals. SUN5 variants lead to absent, significantly reduced, or truncated SUN5, and certain variants altered SUN5 distribution in the head-tail junction of the sperm. In summary, these results demonstrate that biallelic SUN5 mutations cause male infertility due to autosomal-recessive acephalic spermatozoa syndrome.