标题：Novel Mutations in CFAP44 and CFAP43 Cause Multiple Morphological Abnormalities of the Sperm Flagella (MMAF)
作者：Sha, Yan-Wei; Wang, Xiong; Xu, Xiaohui; Su, Zhi-Ying; Cui, Yuanqing; Mei, Li-Bin; Huang, Xian-Jing; Chen, Jie; He, Xue-Mei; Ji, Zhi- 更多 作者机构：[Sha, Yan-Wei; Su, Zhi-Ying; Mei, Li-Bin; Huang, Xian-Jing; He, Xue-Mei; Ji, Zhi-Yong; Li, Ping] Xiamen Matern & Child Care Hosp, Dept Reprod Med, Xia 更多
通讯作者：Li, P;Yang, XY;Li, L
通讯作者地址：[Li, P]Xiamen Matern & Child Care Hosp, Dept Reprod Med, Xiamen 361005, Fujian, Peoples R China;[Yang, XY]Nanjing Med Univ, Dept Reprod Med, Hosp Affi 更多
关键词：multiple morphological abnormalities of the sperm flagella; MMAF;; CFAP44; CFAP43; consanguineous family; whole exome sequencing; dysplasia; of the fibrous sheath
摘要：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.