Patient with CATSPER3 mutations-related failure of sperm acrosome reaction with successful pregnancy outcome from intracytoplasmic sperm injection (ICSI).

Purpose This study is intended to investigate the candidate pathogenic gene in a patient with primary infertility but without the defect in routine semen parameters from a consanguineous family and explore the potential impacts of mutations on assisted reproductive technology outcome. Methods Whole-exome sequencing (WES) was carried out. A variant in his family found by WES was verified by Sanger sequencing. Intracytoplasmic sperm injection (ICSI) was applied to obtain a successful outcome. Results A Cation Channel of Sperm 3(CATSPER3) homozygous variant (NM_ 178019.3:exon5:c.707T>A, p.L236*) was identified for the first time. The anti-CD46 immunofluorescence analysis revealed the failure of sperm acrosome reaction (AR) caused by the mutation. ICSI treatment was successful. Conclusion This is the first report of a homozygous pathogenic CATSPER3 mutation. This mutation may cause male infertility with the failure of AR but without the defect in routine semen parameters. ICSI was supposed to be the most appropriate therapy.