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

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...

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...

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

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...

Molecular characterization of HOXA13 polyalanine expansion proteins in hand-foot-genital syndrome.

We report on a father and daughter with hand-foot-genital syndrome (HFGS) with typical skeletal and genitourinary anomalies due to a 14-residue polyalanine expansion in HOXA13. This is the largest (32 residues) polyalanine tract so far described for any polyalanine mutant protein. Polyalanine expansion results in protein misfolding, cytoplasmic aggregation and degradation; however, HOXA13 polya...