Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract

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 repeat expansion mutations in the HOXD13 gene in Pakistani families with synpolydactyly.

To the Editor : Synpolydactyly (SPD; MIM 186000) is a rare autosomal dominant limb deformity, with a distinctive combination of syndactyly and polydactyly. The main features of SPD are the webbing of the Third or Fourth fingers and Fourth or Fifth toes, with partial or complete digital duplication within the syndactylous web (1, 2). Currently, SPD is classified into three types, SPD1–SPD3. Of t...

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

Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families.

Synpolydactyly (SPD) is a limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance. We have recently mapped this locus centromeric to the HOXD8 intragenic marker and suggested the HOXD13 gene as a potential candidate for this condition. The genomic structure of HOXD13 established in thi...

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

Polyalanine expansion diseases are proposed to result from unequal crossover of sister chromatids that increases the number of repeats. In this report we suggest an alternative mechanism we put forward while we investigated a new spontaneous mutant that we named "Dyc" for "Digit in Y and Carpe" phenotype. Phenotypic analysis revealed an abnormal limb patterning similar to that of the human inhe...