This finding expands the spectrum of DNA damage repair syndromes to include XRCC4 deficiency causing severe postnatal growth failure, microcephaly, gonadal failure, metabolic syndrome, and possibly tumor predisposition.
Silver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic features and is frequently caused by hypomethylation (epimutation) of the H19-DMR.
The potential vital biological role of VPS26C, the nature of the variant which is predicted to result in loss-of-function, expression studies revealing significant reduction in the mutant transcript, the co-segregation of the homozygous variant with the phenotype in two affected individuals all support that VPS26C is a novel gene associated with a previously unrecognized syndrome characterized by neurodevelopmental deficits, growth failure, skeletal abnormalities, and distinctive facial features.This article is protected by copyright.All rights reserved.