Rare missense variants in NECTIN1 alter local protein structure and may contribute to non-syndromic cleft lip with or without palate.

Rare missense variants in NECTIN1, including p.(Arg199Gln) and p.(Gly44Ser), may influence protein structure and contribute to non-syndromic cleft lip with or without palate.

• Why it matters: Understanding genetic factors in orofacial clefts is crucial, especially in high-prevalence regions like Patagonia, where the role of NECTIN1 remains unclear. Identifying genetic contributors can improve diagnosis and potential interventions for this congenital anomaly.
• What they did: The study genotyped 132 families for two NECTIN1 variants and sequenced all six exons in 116 probands, followed by molecular modeling to assess structural impacts of identified variants.
• The result: Two rare heterozygous variants were predicted to alter local protein dynamics and glycosylation, suggesting that such rare variants may influence disease susceptibility in orofacial clefts.