SPATA16 – Globozoospermia (Spermatogenic Failure 6)

Autosomal recessive globozoospermia (MONDO:0007060) has been linked to SPATA16 (HGNC:29935) in a limited number of cases. Two unrelated patients of Tunisian origin were found to harbor a homozygous deletion spanning the first coding exon of SPATA16, suggesting a founder effect (PMID:27086357). No additional familial segregation data are available, and a cohort of 18 Italian globozoospermic men showed no pathogenic SPATA16 variants, indicating locus heterogeneity (PMID:34209343).

Functional interrogation via Glutathione S-transferase pull-down identified SPATA16 interaction partners, supporting a role in acrosome biogenesis, but no direct loss-of-function assays or model organism studies have been reported ([PMID:27086357]). The scarcity of probands and lack of segregation or in vivo validation constrain the current clinical validity to a Limited classification. Further studies are required to define the penetrance and spectrum of SPATA16 variants. Key Take-home: SPATA16 testing may be considered after exclusion of DPY19L2 defects, particularly in patients of specific ancestral backgrounds, but its standalone diagnostic utility remains limited.

References

• Journal of assisted reproduction and genetics • 2016 • A new mutation identified in SPATA16 in two globozoospermic patients. PMID:27086357
• Life (Basel, Switzerland) • 2021 • Molecular Analysis of DPY19L2, PICK1 and SPATA16 in Italian Unrelated Globozoospermic Men. PMID:34209343
• Human reproduction update • 2015 • Teratozoospermia: spotlight on the main genetic actors in the human. PMID:25888788

Evidence Based Scoring (AI generated)