A classification system for split-hand/ foot malformation (SHFM): A proposal based on 3 pedigrees with WNT10B mutations.

A classification system for split-hand/ foot malformation (SHFM): A proposal based on 3 pedigrees with WNT10B mutations.
Eur J Med Genet. 2019 Aug 14;:103738
Authors: Al Ghamdi MA, Al-Qattan MM, Hadidi A, Alabdulrahman A, Almuzzaini B, Alatwi N, AlBalwi MA
Abstract
SHFM6 (OMIM 225300) is caused by WNT10B pathogenic variants (12q13.12). It is one of the rarest forms of SHFM; with only seven pathogenic variants described in the world literature. Furthermore, it has not been determined if SHFM6 has specific phenotypic characteristics. In this paper, we present a case series of three unrelated families with SHFM6 caused by three novel WNT10B pathogenic variants. The index patient of the first family was homozygous for the nonsense variant c.676C > T (p.Arg226*) in the WNT10B gene. The index case of the second family had a homozygous splice variant c.338-1G > C in the WNT10B gene. Finally, the index case of the third family carried two different variants in the WNT10B gene: A nonsense variant (p.Arg226*), and a missense variant (p.Gln86Pro). The latter represents the first compound heterozygous pathogenic variant related to SHFM6. We also offer a classification system for the hand/foot defects to illustrate the specific phenotypic characteristics of SHFM6. Based on this classification and a review of all previously reported cases, we demonstrate that SHFM6 caused by WNT10B pathogenic variants have the following characteristics...

Source: European Journal of Medical Genetics - August 13, 2019 Category: Genetics & Stem Cells Authors: Al Ghamdi MA, Al-Qattan MM, Hadidi A, Alabdulrahman A, Almuzzaini B, Alatwi N, AlBalwi MA Tags: Eur J Med Genet Source Type: research