HOXD13

HOXD13, the homeobox-containing gene located at the most 5’ end of the HOXD cluster, plays a critical role in limb development. It has been shown that mutations in human HOXD13 can give rise to limb malformations, with variable expressivity and a wide spectrum of clinical manifestations.

Polyalanine expansions in HOXD13 cause synpolydactyly, whereas amino acid substitutions in the homeodomain are associated with brachydactyly types D and E.

Pathology

 fused in the HOXD13-NUP98 fusion gene in acute myeloid leukemia

 HOXD13 germline mutations (polyalanine repeat expansion) in HOXD13 limb morphopathies

• synpolydactyly (MIM.186000) with or without foot anomaly (hand/foot malformation with syndactyly and polydactyly, brachydactyly, hypodactyly)
• synpolydactyly type Vordingborg (12116248)
• brachydactyly types D (MIM.113200) and E (MIM.113300) (12649808)
• syndactyly type V (17236141)
• brachydactyly type A4 (17236141)
• triphalangeal thumb-brachyectrodactyly syndrome (12382951)

See also

 polyalanine repeat expansions

References

 Zhao X, Sun M, Zhao J, Leyva JA, Zhu H, Yang W, Zeng X, Ao Y, Liu Q, Liu G, Lo WH, Jabs EW, Amzel LM, Shan X, Zhang X. Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome. Am J Hum Genet. 2007 Feb;80(2):361-71. PMID: 17236141

 Kjaer KW, Hedeboe J, Bugge M, Hansen C, Friis-Henriksen K, Vestergaard MB, Tommerup N, Opitz JM. HOXD13 polyalanine tract expansion in classical synpolydactyly type Vordingborg. Am J Med Genet. 2002 Jun 15;110(2):116-21. PMID: 12116248

 Pérez-Cabrera A, Kofman-Alfaro S, Zenteno JC. Mutational analysis of HOXD13 and HOXA13 genes in the triphalangeal thumb-brachyectrodactyly syndrome. J Orthop Res. 2002 Sep;20(5):899-901. PMID: 12382951