• PMID: 29277146
• Gene Name: CFAP43
• Condition: Multiple morphological abnormalities of the sperm flagella (MMAF)
• Association: Associated
• Mutation: CFAP44 mutations (3 homozygous: c.2935_2944del: p.D979*, c.T1769A: p.L590Q, c.2005_2006del: p.M669Vfs*13; and putative compound heterozygous: c.G3262A: p.G1088S and c.C1718A: p.P573H.), CFAP43 (c.3661-2A>-)
• Population size: 27
• Population details: 27 patients with MMAF
• Sex: Male
• Infertility type: Male infertility
• Associated genes: CFAP43, CFAP44
• Other associated phenotypes: Multiple morphological abnormalities of the sperm flagella (MMAF)

Novel Mutations in CFAP44 and CFAP43 Cause Multiple Morphological Abnormalities of the Sperm Flagella (MMAF)

Sha YW, Wang X, Xu X, Su ZY, Cui Y, Mei LB, Huang XJ, Chen J, He XM, Ji ZY, Bao H, Yang X, Li P, Li L.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a rare disease that causes primary infertility. However, the genetic causes for approximately half of MMAF cases are unknown. Whole exome sequencing analysis of the 27 patients with MMAF identified several CFAP44 mutations (3 homozygous: c.2935_2944del: p.D979*, c.T1769A: p.L590Q, c.2005_2006del: p.M669Vfs*13; and putative compound heterozygous: c.G3262A: p.G1088S and c.C1718A: p.P573H.) and CFAP43 acceptor splice-site deletion (c.3661-2A>-) mutations in 5 and 1 patients, respectively. Real-time quantitative polymerase chain reaction assays also demonstrated that CFAP44 expression was very weak in patient (P)1 and P3, and CFAP43 expression was lower in P6 than in the control. Immunofluorescence analysis of CFAP43 showed lower CFAP43 protein expression levels in P6 than in the normal control. This study demonstrated that biallelic mutations in CFAP44 and CFAP43 cause MMAF. These results provide researchers with a new insight to understand the genetic etiology of MMAF and to identify new loci for genetic counselling of MMAF. FAU - Sha, Yan-Wei AU - Sha YW AD - 1 Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, Fujian, China. FAU - Wang, Xiong AU - Wang X AD - 2 Department of Surgery, Medical College of Shandong University, Jinan, Shandong, China. AD - 3 Reproductive Medicine Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. FAU - Xu, Xiaohui AU - Xu X AD - 4 School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China. FAU - Su, Zhi-Ying AU - Su ZY AD - 1 Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, Fujian, China. FAU - Cui, Yuanqing AU - Cui Y AD - 3 Reproductive Medicine Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. FAU - Mei, Li-Bin AU - Mei LB AD - 1 Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, Fujian, China. FAU - Huang, Xian-Jing AU - Huang XJ AD - 1 Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, Fujian, China. FAU - Chen, Jie AU - Chen J AD - 3 Reproductive Medicine Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. FAU - He, Xue-Mei AU - He XM AD - 1 Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, Fujian, China. FAU - Ji, Zhi-Yong AU - Ji ZY AD - 1 Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, Fujian, China. FAU - Bao, Hongchu AU - Bao H AD - 3 Reproductive Medicine Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. FAU - Yang, Xiaoyu AU - Yang X AD - 5 Department of Reproductive Medicine, the First Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China. FAU - Li, Ping AU - Li P AD - 1 Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, Fujian, China.