Novel Biallelic Mutation c.131G>T in MEI1 Causes Meiotic Arrest and Nonobstructive Azoospermia

Nonobstructive azoospermia (NOA) is considered to be the most severe form of male infertility. Meiotic arrest is one of the major causes of NOA and can be caused by single gene mutations. Here, a novel homozygous missense mutation (c.131G>T) in the MEI1 gene was identified through whole exome sequencing in a Chinese men with NOA caused by meiotic arrest. Bioinformatics and genetic analysis predicted that this novel mutation may be deleterious. Our findings confirm that spermatogenesis is arrested at the primary spermatocyte stage, with defective programed DNA double-strand breaks (DSBs) formation. In vitro functional analysis revealed that the defects of DSBs formation may be a result of a lower expression level of MEI1 protein in the mutant. Therefore, the NOA in this patient is likely caused by the single novel mutation in the MEI1 gene leading to meiotic arrest. Our report expands the mutation spectrum of MEI1 and provides new evidence that the MEI1 gene may serve as a diagnostic marker for genetic counseling in NOA patients.