A clinical and multi ‑omics study of Van der Woude syndrome in three generations of a Chinese family.

A clinical and multi‑omics study of Van der Woude syndrome in three generations of a Chinese family. Mol Med Rep. 2020 Jul 28;: Authors: Yang K, Dong XY, Wu J, Zhu JJ, Tan Y, Yan YS, Lin L, Zhang DL Abstract Previous studies have suggested that pathogenic variants in interferon regulatoryse factor 6 (IRF6) can account for almost 70% of familial Van der Woude Syndrome (VWS) cases. However, gene modifiers that account for the phenotypic variability of IRF6 in the context of VWS remain poorly characterized. The aim of this study was to report a family with VWS with variable expressivity and to identify the genetic cause. A 4‑month‑old boy initially presented with cleft palate and bilateral lower lip pits. Examination of his family history identified similar, albeit milder, clinical features in another four family members, including bilateral lower lip pits and/or hypodontia. Peripheral blood samples of eight members in this three‑generation family were subsequently collected, and whole‑exome sequencing was performed to detect pathogenic variants. A heterozygous missense IRF6 variant with a c.1198C>T change in exon 9 (resulting in an R400W change at the amino acid level) was detected in five affected subjects, but not in the other three unaffected subjects. Moreover, subsequent structural analysis was indicative of damaged stability to the structure in the mutant IRF protein. Whole‑transcriptome sequencing, expression ana...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research