Novel Bi-Allelic Variants of FANCM Cause Sertoli Cell-Only Syndrome and Non-Obstructive Azoospermia

Yuxiang Zhang; Peng Li; Nachuan Liu; Tao Jing; Zhiyong Ji; Chao Yang; Liangyu Zhao; Ruhui Tian; Huixing Chen; Yuhua Huang; Erlei Zhi; Ningjing Ou; Haowei Bai; Yuchuan Zhou; Zheng Li; Chencheng Yao

doi:10.3389/fgene.2021.799886

Novel Bi-Allelic Variants of FANCM Cause Sertoli Cell-Only Syndrome and Non-Obstructive Azoospermia

Front Genet. 2021 Dec 15:12:799886. doi: 10.3389/fgene.2021.799886. eCollection 2021.

Authors

Yuxiang Zhang^{1

2}, Peng Li^{1

2}, Nachuan Liu^{1

2}, Tao Jing^{1

2}, Zhiyong Ji³, Chao Yang^{1

2}, Liangyu Zhao^{1

2}, Ruhui Tian^{1

2}, Huixing Chen^{1

2}, Yuhua Huang^{1

2}, Erlei Zhi^{1

2}, Ningjing Ou³, Haowei Bai^{1

2}, Yuchuan Zhou⁴, Zheng Li^{1

2}, Chencheng Yao^{1

2}

Affiliations

¹ Depart. of Andrology, Center for Men's Health, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Lab of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
⁴ The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Non-obstructive azoospermia (NOA) is the most severe disease in male infertility, but the genetic causes for the majority of NOA remain unknown. FANCM is a member of Fanconi Anemia (FA) core complex, whose defects are associated with cell hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents. It was reported that variants in FANCM (MIM: 609644) might cause azoospermia or oligospermia. However, there is still a lack of evidence to explain the association between different FANCM variants and male infertility phenotypes. Herein, we identified compound heterozygous variants in FANCM in two NOA-affected brothers (c. 1778delG:p. R593Qfs*76 and c. 1663G > T:p. V555F), and a homozygous variant in FANCM (c. 1972C > T:p. R658X) in a sporadic case with NOA, respectively. H&E staining and immunohistochemistry showed Sertoli cell-only Syndrome (SCOS) in the three patients with NOA. Collectively, our study expands the knowledge of variants in FANCM, and provides a new insight to understand the genetic etiology of NOA.

Keywords: FANCM; Sertoli cell-only syndrome; gene mutation; male infertility; non-obstructive azoospermia.