Novel mutations in ZMYND15 expand the phenotypic spectrum to acephalic spermatozoa: abnormal sperm head-tail connection mediated by SUN5.
Qian-Jun Zhang, Hao Lin, Rui-Long Hao et al.
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Case in brief
Two infertile patients had extremely low sperm counts, poor motility, and numerous spermatozoa without heads. Whole-exome sequencing identified homozygous truncating ZMYND15 variants in both. Sperm studies showed abnormal neck structures, absent mitochondrial sheaths, failed acrosome formation, and missing central microtubules; laboratory experiments also found reduced mutant protein expression and degradation. ZMYND15 interacted directly with SUN5, which is important for the sperm head–tail connection. After intracytoplasmic sperm injection, one patient had a live birth and the other an early miscarriage.
What made this case unusual
The report links ZMYND15 mutations to acephalic spermatozoa and an abnormal sperm head–tail connection, extending the described phenotype associated with this gene.
Diagnostic / clinical pearl
In men with numerous headless spermatozoa, consider genetic evaluation for ZMYND15 variants; sperm ultrastructure and immunofluorescence can help characterize the associated neck and flagellar abnormalities.