• PMID: 31676830
• Gene Name: DNAH6
• Condition: Primary infertility due to multiple morphological abnormalities of the sperm flagella (MMAF)
• Association: Associated
• Mutation: c.6582?C?>?A, p. D2194E and c.11258?G?>?A, p. G3753D
• Population size: 10
• Population details: 10 cases
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

Identification of DNAH6 mutations in infertile men with multiple morphological abnormalities of the sperm flagella

Tu C, Nie H, Meng L, Yuan S, He W, Luo A, Li H, Li W, Du J, Lu G, Lin G, Tan YQ.

Male infertility due to spermatogenesis defects affects millions of men worldwide. However, the genetic etiology of the vast majority remains unclear. Here we describe three men with primary infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) from two unrelated Han Chinese families. We performed whole-exome sequencing (WES) and Sanger sequencing on the proband of family 1, and found that he carried novel compound heterozygous missense mutations in dynein axonemal heavy chain 6 (DNAH6) that resulted in the substitution of a conserved amino acid residue and co-segregated with the MMAF phenotype in this family. Papanicolaou staining and transmission electron microscopy analysis revealed morphological and ultrastructural abnormalities in the sperm flagella in carriers of these genetic variants. Immunostaining experiments showed that DNAH6 was localized in the sperm tail. This is the first report identifying novel recessive mutations in DNAH6 as a cause of MMAF. These findings expand the spectrum of known MMAF mutations and phenotypes and provide information that can be useful for genetic and reproductive counseling of MMAF patients. FAU - Tu, Chaofeng AU - Tu C AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. AD - National Engineering and Research Center of Human Stem Cell, Changsha, Hunan, 410078, China. FAU - Nie, Hongchuan AU - Nie H AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. AD - National Engineering and Research Center of Human Stem Cell, Changsha, Hunan, 410078, China. FAU - Meng, Lanlan AU - Meng L AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. FAU - Yuan, Shimin AU - Yuan S AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. FAU - He, Wenbin AU - He W AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. AD - National Engineering and Research Center of Human Stem Cell, Changsha, Hunan, 410078, China. FAU - Luo, Aixiang AU - Luo A AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. FAU - Li, Haiyu AU - Li H AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. FAU - Li, Wen AU - Li W AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. AD - National Engineering and Research Center of Human Stem Cell, Changsha, Hunan, 410078, China. FAU - Du, Juan AU - Du J AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. AD - National Engineering and Research Center of Human Stem Cell, Changsha, Hunan, 410078, China. FAU - Lu, Guangxiu AU - Lu G AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. AD - National Engineering and Research Center of Human Stem Cell, Changsha, Hunan, 410078, China. FAU - Lin, Ge AU - Lin G AD - Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, 410078, China. AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, 410078, China. AD - National Engineering and Research Center of Human Stem Cell, Changsha, Hunan, 410078, China.