Identification of a Novel Biallelic CFAP119 Variant in an Infertile Man with Asthenoteratozoospermia

다국어 초록 (Multilingual Abstract)

Purpose: Infertility affects approximately 10% to 20% of couples globally, with male factors contributing to nearly 50% of infertility cases. Among these, represents a severe form of male infertility, though its etiology remains largely unknown.
CFAP119 has been implicated in sperm flagellar formation and is essential for fertility in mice; however, its role in human fertility has not been established.
Materials and Methods: Whole exome sequencing (WES) was performed to identify pathogenic variants in a patient with asthenoteratozoospermia, and the functional impact of the mutations was assessed using in silico and in vitro analysis. Intracytoplasmic sperm injection (ICSI) was applied to assist fertilization for the patient.
Results: In this study, we identified a novel biallelic missense mutation in CFAP119 in a patient with asthenoteratozoospermia through WES. Immunofluorescence staining and western blotting demonstrated that the variants impaired the protein expression.
Morphological analysis of the patient’s sperm revealed severely malformed tails and head abnormalities. Ultrastructural examination also confirmed significant defects in the sperm flagella “9+2” microtubule composition. Additionally, in silico analysis predicted interactions between CFAP119 and flagellum development related proteins, including CFAP74, CFAP221, which were further validated by co-immunoprecipitation. Notably, the patient with the CFAP119 mutation successfully achieved healthy offspring through ICSI.
Conclusions: Our findings revealed novel pathogenic variants within CFAP119 in patient with asthenoteratozoospermia, expanding our understanding of the genetic etiology of male infertility and providing valuable insights for future diagnostic and therapeutic approaches.