DDX3Y loss-of-function variant in AZFa-like non-obstructive azoospermia highlights gaps in current Y-chromosome microdeletion testing.
Florence Abou, Netanel Waldenberg, Shany Kravat et al.
✦ AI-curated · Sources linked
Case in brief
A man with idiopathic non-obstructive azoospermia presented with an AZFa-like phenotype, characterized by elevated FSH and a normal karyotype. Standard AZFa deletion testing was negative, and microdissection testicular sperm extraction revealed complete Sertoli-cell-only syndrome with no sperm retrieved. Whole exome sequencing later identified a novel likely pathogenic loss-of-function variant in DDX3Y, which was undetectable by routine testing.
What made this case unusual
The case highlights a loss-of-function variant in DDX3Y, a critical spermatogenic factor, which was not identified by standard AZFa microdeletion testing, illustrating a significant diagnostic gap.
Diagnostic / clinical pearl
Clinicians should consider DDX3Y analysis in men with non-obstructive azoospermia and an AZFa-like phenotype, especially when standard testing yields negative results.
Why it matters
This case underscores the limitations of current Y-chromosome microdeletion testing and the potential need for expanded genetic testing to improve diagnosis and management in azoospermia.