CCDC40 mutation as a cause of infertility in a Chinese family with primary ciliary dyskinesia.

Trial Design: Primary ciliary dyskinesia (PCD) is a genetical disease that inherited in an autosomal-recessive way. Its clinical manifestations (such as male infertility) are mainly caused by defects of motion-related cilia that encoded by mutated genes. Although some mutation has been verified, a number of mutations of PCD remain elusive. The main purpose of this study is to identify mutant genes in a Chinese family with PCD, and to verify the safety and effectiveness of intracytoplasmic sperm injection (ICSI) of infertility caused by PCD.

Methods: Imaging examination was used to exclude pulmonary inflammation and visceral translocation. Semen analysis was used to assess the quality of the proband's sperm. Transmission electron microscopy (TEM) was conducted to assess the ultrastructure of flagella and cilia. Targeted next generation sequencing and Sanger sequencing and qPCR (real-time quantitative polymerase chain reaction detecting system) were applied to identified mutation of Chinese Family suspected of having PCD. Viable sperm were selected by hypo-osmotic swelling test (HOST) for ICSI.

Results: We report 2 novel mutations in CCDC40 gene (c.1259delA and EX17_20 deletion) resulted in immobility of sperm and infertility of the proband. These mutations were confirmed in the proband's sister (heterozygous) and his parents (recessive carrier) by Sanger sequencing and qPCR. All the spermatozoa from the proband were immotile. Ultrastructural defects were found in flagella and cilia of proband and his sister. Viable sperms were selected by HOST for ICSI and fertilized 9 of 21 eggs. Two frozen embryos were transplanted and a healthy 3500 g boy was delivered at 40 + 4 weeks' gestation. And then, we summarized the genes related to PCD and the mutant sites of CCDC40 gene.

Conclusion: We reported 2 novel mutants in CCDC40 gene (c.1259delA and EX17_20 deletion), which could be candidates for genetic diagnosis in PCD patients. The combination of targeted next generation sequencing and Sanger sequencing may be a useful tool to diagnose PCD. ICSI is a considerable method in treatment of infertility caused by PCD.