|
|||||
|
|
An M1AP homozygous splice-site mutation associated with severe oligozoospermia in a consanguineous family |
|
| Authors: | Chaofeng Tu Ying Wang Hongchuan Nie Lanlan Meng Weili Wang Yong Li Dongyan Li Huan Zhang Guangxiu Lu Ge Lin Yue-Qiu Tan Juan Du |
| Affiliation: | 1. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China Key Lab of MOE for Development Biology and Protein Chemistry, The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha, China;2. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China;3. Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China;4. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China |
| Abstract: | Severe oligozoospermia (SO) is an important cause of male infertility. Its etiology and pathogenesis are associated with genetic abnormalities; however, the genetic causes of the majority of idiopathic human SO remain unclear. Here, we report a homozygous splice-site mutation in M1AP (meiosis 1 associated protein; NM_138804, c.1435-1G>A) observed in a patient with SO from a consanguineous Han Chinese family. His parents and fertile brother were heterozygous for the mutation. The splice variant led to a lack of M1AP protein in the patient's spermatozoa. Ultrastructural and immunostaining analyses of patient's spermatozoa showed highly aberrant swollen mitochondrial sheaths with normal axonemal structures. Subsequent mutation screening identified three additional heterozygous M1AP variants in 4/243 subjects with idiopathic SO, but no M1AP variants among 223 fertile subjects. Additionally, a previously study reported that M1ap knock-out mice exhibited SO due to meiotic arrest. Hence, our findings indicate that M1AP mutation might represent novel genetic alteration responsible for human SO. |
| Keywords: | M1AP male infertility meiosis severe oligozoospermia whole-exome sequencing |