Abstract
BackgroundMultiple morphological abnormalities of the sperm flagella (MMAF) is a kind of severe teratozoospermia. Patients with the MMAF phenotype are infertile and present aberrant spermatozoa with absent, short, coiled, bent and/or irregular flagella. Mutations in several genes can explain approximately 30%–50% of MMAF cases and more genetic pathogenies need to be explored. SPEF2 was previously demonstrated to play an essential role in sperm tail development in mice and pig. Dysfunctional mutations in SPEF2 impair sperm motility and cause a short-tail phenotype in both animal models.ObjectiveBased on 42 patients with severe infertility and MMAF phenotype, we explored the new genetic cause of human MMAF phenotype.Methods and resultsBy screening gene variants in 42 patients with MMAF using whole exome sequencing, we identified the c. 12delC, c. 1745-2A > G, c. 4102 G > T and c. 4323dupA mutations in the SPEF2 gene from two patients. Both of these mutations are rare and potentially deleterious. Transmission electron microscope (TEM) analysis showed a disrupted axonemal structure with mitochondrial sheath defects in the patients’ spermatozoa. The SPEF2 protein level was significantly decreased in the spermatozoa of the patients revealed by Western blot (WB) and immunofluorescence (IF) analyses.ConclusionOur experimental findings indicate that loss-of-function mutations in the SPEF2 gene can cause the MMAF phenotype in human.
Funder
the Medicine and Health Science Technology Development Project of Shandong Province
Natural Science Foundation of Shandong Province
the National Natural Science Foundation of China
the Science Technology Guidance Project of Fujian Province
The open project of Key Laboratory of Male Reproduction and Genetics, National Health and Family Planning Commission
the Linqiaozhi Funding Supporting Youth Project of Xiamen Maternity and Child Care Hospital
Subject
Genetics (clinical),Genetics
Cited by
68 articles.
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