Mutation of GALNTL5 gene identified in patients diagnosed with asthenozoospermia.

Asthenozoospermia is commonly observed in infertile men. However, very few causative gene mutations have been identified because an efficient detection method has not been established. We previously identified a patient with asthenozoospermia carrying a heterozygous point deletion in GALNTL5 by detecting an abnormal reduction in the abundance of GALNTL5 and other marker proteins. To identify other mutations in GALNTL5, we screened sperm samples from 208 infertile men mainly diagnosed with asthenozoospermia using the same method, and conducted next-generation sequencing. Consequently, another case of GALNTL5 mutation was detected only in sperm at a low frequency but not in the somatic blood cells of a patient diagnosed with asthenozoospermia. In this patient, sperm motility improved and the mutation disappeared at 2 years after the first observation. In this man, carrying a heterozygotic deficiency of GALNTL5, the swim-up method was useful to concentrate the spermatozoa without mutation. Intracytoplasmic sperm injection of the selected motile spermatozoa into oocytes of the patient's partner resulted in successful conception, and a female child was safely delivered. These results suggest the feasibility of our approach for the screening and treatment of asthenozoospermia associated with GALNTL5 mutation.