HOXD13 polyalanine tract expansion in classical synpolydactyly type Vordingborg

Abstract

In 1927, Oluf Thomsen, in a classic paper, described a seven-generation family with autosomal dominant axial synpolydactyly (SPD)--the Vordingborgtyp of axis duplication and dysostosis. Expansion of a polyalanine tract in the HOXD13 gene is known to cause synpolydactyly. We have rediscovered part of the family described by Thomsen, and detected a 9 triplet polyalanine expansion within HOXD13segregating with the disorder. The phenotypic spectrum in mutation carriers ranged from severe to inapparent bone malformations. In the latter case, only dermatoglyphics revealed the genetic status.

A novel type of autosomal recessive syndactyly: Clinical and molecular studies in a family of Pakistani origin

“…Expansions of a polyalanine stretch in homeobox gene HOXD13 at 2q31 have been implicated in this type [Akarsu et al, 1996;Muragaki et al, 1996;Kjaer et al, 2002]. Studies have shown that type I syndactyly is also linked to the long arm of chromosome 2, in close vicinity of SPD locus at 2q34-q36 [Bosse et al, 2000] and that, there is genetic homogeneity in syndactyly type I [Ghadami et al, 2001].…”

Breakpoints around the HOXD cluster result in various limb malformations

“…5 Similar pathological polyalanine tract expansions in HOXD13 have subsequently been reported in other families with SPD. [6][7][8] Intragenic frameshift deletions in HOXD13, predicted to result in truncated proteins, and also an acceptor splice site mutation and a missense mutation in exon 2 of HOXD13, cause an atypical form of SPD. [9][10][11][12] Interestingly, a different missense mutation in the same exon has been found in a family with a dominantly inherited combination of brachydactyly and polydactyly.…”

Type II familial synpolydactyly: report on two families with an emphasis on variations of expression

“…Sayli et al 10 showed that some family members may show polydactyly of the little finger and this was seen in one child of the first family. Several authors 5,11,12 showed that clinodactyly of the little finger may be a concurrent or isolated feature, indicating that the responsible gene may be expressed as an isolated clinodactyly and this was seen in the parents of the second family. Finally, Akarsu et al 1 and Muragaki et al 7 have described the 'homozygous' phenotype that is characterized by short hands, polygonal metacarpals/metatarsals, accessory carpal bones and tarsometatarsal fusion.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12] It is characterized by bilateral synpolydactyly of the third web spaces of the hands and bilateral synpolydactyly of the fourth web spaces of the feet. It is inherited as autosomal dominant and the mutation has been localized to 2q31 (HOXD13).…”

“…It is inherited as autosomal dominant and the mutation has been localized to 2q31 (HOXD13). [5][6][7] In this paper, we report on two families with an emphasis on variations of expression of this rare form of inherited nonsyndromal syndactyly. These variations have not been previously reviewed in the literature.…”