Functional classification and mutation analysis of a synpolydactyly kindred

Abstract

The aim of the present study was to analyze a congenital syndactyly/polydactyly kindred and propose a new functional classification method of clinical significance. The modes of inheritance and mutational mechanisms were also determined using genetic analyses. Hand and foot anatomy and functions were measured using photographic images, X-ray imaging and grip ability tests. Genetic analysis comprised the genotyping of polymorphic microsatellite markers at known polydactyly-associated loci and the sequencing of the candidate gene. A functional classification system was devised to divide the clinical features into three types, which included mild, moderate or severe deformity. The family was concluded to have syndactyly type II with autosomal dominant inheritance. The microsatellites, D2S2310 and D2S2314, at the 2q31–32 chromosome, which have previously been associated with synpolydactyly type I, were found to be associated with the disorder in the current family. A 27-bp insertion mutation was identified in the affected individuals in the HOXD13 gene at this locus. The insertion added a further nine alanine residues to the polyalanine stretch within the encoded protein. In conclusion, the functional classification method described in the present study may be used to guide surgical approaches to treatment. A family was identified in whom expansion of the polyalanine tract in the HOXD13 gene causes autosomal dominant hereditary synpolydactyly.

Long‐read whole genome sequencing reveals HOXD13 alterations in synpolydactyly

“…Homozygous and heterozygous nonsense variants affecting the DNA binding site in the homeodomain of HOXD13 lead to a variety of limb abnormalities and other skeletal defects with reduced penetrance (Jamsheer et al, 2012; Kurban et al, 2011; Low & Newbury‐Ecob, 2012). In addition, variants in the polyalanine tract domains of HOXD13 result in SPD phenotypes (Akarsu et al, 1996; Albrecht et al, 2004; Brison et al, 2012; Gong et al, 2011; Goodman et al, 1997; Kjaer et al, 2005, 2002; Tuzel et al, 2007; Zaib et al, 2019; Zhou et al, 2014). However, alterations outside of these domains can cause a wide spectrum of clinical features making the differential diagnosis complicated.…”

A novel microdeletion upstream of HOXD13 in a Chinese family with synpolydactyly

“…The type II syndactyly, also called synpolydactyly (SPD), with typical features of fusion of 3/4 fingers and 4/5 toes, with partial or complete digital duplication within the syndactylous web (Malik & Grzeschik, 2008; Merlob & Grunebaum, 1986). Three types of SPD have been designated as SPD1, SPD2, and SPD3 according to the disease‐causing variants in the HOXD13 gene, FBLN1 gene, and a genetic locus within 14q11.2‐q12, separately (Brison et al, 2014; Malik & Grzeschik, 2008; Zhou et al, 2014).…”

Xantoma tendinoso normolipémico múltiple en coexistencia con glaucoma terminal bilateral y sindactilia

“…La sindactilia es la fusión del tejido blando y/o hueso entre dedos adyacentes de las manos o pies, provocando una ausencia total o parcial del espacio entre dos dedos que puede presentarse en el recién nacido, por una alteración del desarrollo entre el primer y segundo mes de vida intrauterina o en la edad infantil, secundario a un trauma como quemaduras, o una secuela de heridas complejas de manos o pies que comprometen cicatricialmente los espacios interdigitales (4) .…”