A Synonymous Exonic Splice Silencer Variant in IRF6 as a Novel and Cryptic Cause of Non-Syndromic Cleft Lip and Palate.

ABSTRACT: Missense, nonsense, splice site and regulatory region variants in interferon regulatory factor 6 (IRF6) have been shown to contribute to both syndromic and non-syndromic forms of cleft lip and/or palate (CL/P). We report the diagnostic evaluation of a complex multigeneration family of Honduran ancestry with a pedigree structure consistent with autosomal-dominant inheritance with both incomplete penetrance and variable expressivity. The proband's grandmother bore children with two partners and CL/P segregates on both sides of each lineage. Through whole-exome sequencing of five members of the family, we identified a single shared synonymous variant, located in the middle of exon 7 of IRF6 (p.Ser307Ser; g.209963979 G>A; c.921C>T). The variant was shown to segregate in the seven

SUBMITTER: Sylvester B 

PROVIDER: S-EPMC7465030 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature