Fork stalling and template switching as a mechanism for polyalanine tract expansion affecting the DYC mutant of HOXD13, a new murine model of synpolydactyly.

Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract.

Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation. Typical cases have 3/4 finger and 4/5 toe syndactyly, with a duplicated digit in the syndactylous web, but incomplete penetrance and variable expressivity are common. The condition has recently been shown to be caused by expansions of an imperfect trinucleotide repeat sequence encoding a 15-residue polyalanine tract in...

Polyalanine expansion in synpolydactyly might result from unequal crossing-over of HOXD13.

The synpolydactyly homolog (spdh) mutation in the mouse – a defect in patterning and growth of limb cartilage elements

We have investigated the recessive mouse mutant synpolydactyly homolog (spdh) as a model for human synpolydactyly (SPD). As in human SPD, the spdh phenotype consists of central polydactyly, syndactyly and brachydactyly and is caused by the expansion of a polyalanine encoding repeat in the 5' region of the Hoxd13 gene. We performed a detailed phenotypic and functional analysis of spdh/spdh embry...

An N-terminal G11A mutation in HOXD13 causes synpolydactyly and interferes with Gli3R function during limb pre-patterning.

Synpolydactyly (SPD) is a distal limb anomaly characterized by incomplete digit separation and the presence of supernumerary digits in the syndactylous web. This phenotype has been associated with mutations in the homeodomain or polyalanine tract of the HOXD13 gene. We identified a novel mutation (G11A) in HOXD13 that is located outside the previously known domains and affects the intracellular...

Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13.

Hox genes encode a highly conserved family of transcription factors with fundamental roles in body patterning during embryogenesis. Studies in mouse and chick have shown that the 5′ HoxD and HoxA genes are critical for vertebrate limb and urogenital tract development. In humans, mutations in HOXD13 and HOXA13 cause the rare dominantly inherited limb malformation syndromes synpolydactyly (SPD, M...