• PMID: 30904354
• Gene Name: CFAP43
• Condition: Multiple morphological abnormalities of the sperm flagella (MMAF)
• Association: Associated
• Mutation: c.1140_1143del: p.Asn380Lysfs*3, c.739A>T: p.Lys247*, c.1474G>C: p.Gln492Arg; c.4600C>G: p.Leu1534Val,
• Population size: 13
• Population details: 13 with MMAF
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

NovelCFAP43 andCFAP44 mutations cause male infertility with multiple morphological abnormalities of the sperm flagella (MMAF)

Wu H, Li W, He X, Liu C, Fang Y, Zhu F, Jiang H, Liu W, Song B, Wang X, Zhou P, Wei Z, Zhang F, Cao Y.

RESEARCH QUESTION: Multiple morphological abnormalities of the sperm flagella (MMAF) comprise a rare congenital disease that can cause primary male infertility. Several pathogenic genes (e.g. AKAP4, DNAH1, CFAP43 and CFAP44) are associated with MMAF but the pathogenic mechanisms have not been elucidated. DESIGN: Whole-exome sequencing (WES) was applied to identify the pathogenic genes in 13 Chinese patients with MMAF; the patients were unrelated but all had consanguineous parents (usually first cousins). Real-time polymerase chain reaction and immunofluorescence staining were employed to assess the pathogenicity of these mutations. RESULTS: Four novel homozygous CFAP43 mutations in four (30.8%) MMAF patients and one novel homozygous CFAP44 mutation in one (7.7%) other case were identified. The four novel homozygous CFAP43 mutations included one frameshift mutation (c.1140_1143del: p.Asn380Lysfs*3), one nonsense mutation (c.739A>T: p.Lys247*) and two missense mutations (c.1474G>C: p.Gln492Arg; c.4600C>G: p.Leu1534Val). The novel mutation in CFAP44 was a homozygous nonsense mutation (c.4963C>T: p.Arg1655*). Co-segregation of the mutations was verified by Sanger sequencing of the families. The relative mRNA expression levels of CFAP43 in patients 1 and 9 and the levels of CFAP44 in patient 5 were significantly lower than those in control sperm samples. Immunofluorescence analysis of CFAP43 showed the protein was absent in the sperm flagella of patients 1 and 9. Furthermore, two previously reported mutations of DNAH1 were also identified in another four (30.8%) patients. CONCLUSIONS: This study demonstrated that CFAP43 and CFAP44 mutations are important causes of MMAF in the Chinese population. These novel mutations broaden the spectrum of CFAP43 and CFAP44 mutations. CI - Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. FAU - Wu, Huan AU - Wu H AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. FAU - Li, Weiyu AU - Li W AD - Obstetrics and Gynecology Hospital, School of Life Sciences, Fudan University, Shanghai 200011, China; NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Fudan University, Shanghai 200032, China. FAU - He, Xiaojin AU - He X AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. FAU - Liu, Chunyu AU - Liu C AD - Obstetrics and Gynecology Hospital, School of Life Sciences, Fudan University, Shanghai 200011, China; NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Fudan University, Shanghai 200032, China. FAU - Fang, Youyan AU - Fang Y AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. FAU - Zhu, Fuxi AU - Zhu F AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. FAU - Jiang, Huanhuan AU - Jiang H AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. FAU - Liu, Wangjie AU - Liu W AD - Obstetrics and Gynecology Hospital, School of Life Sciences, Fudan University, Shanghai 200011, China; NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Fudan University, Shanghai 200032, China. FAU - Song, Bing AU - Song B AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. FAU - Wang, Xue AU - Wang X AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. FAU - Zhou, Ping AU - Zhou P AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. FAU - Wei, Zhaolian AU - Wei Z AD - Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. FAU - Zhang, Feng AU - Zhang F AD - Obstetrics and Gynecology Hospital, School of Life Sciences, Fudan University, Shanghai 200011, China; NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China. Electronic address: zhangfeng@fudan.edu.cn.