title: An acceptor splice site mutation in HOXD13 results in variable hand, but consistent foot malformations.
abstract: HOXD13 is the most 5' of the HOXD cluster of homeobox genes in chromosome band 2q31.1. Heterozygous expansions of a polyalanine tract in HOXD13 are typically associated with synpolydactyly characterized by insertional digit duplication associated with syndactyly. We screened for mutations of HOXD13 in patients with a variety of limb malformations and identified a novel heterozygous mutation (758-2delA) in a three-generation family without the typical synpolydactyly phenotype in the hands, but with bilateral partial duplication of the 2nd metatarsals within the first web space of the feet. This mutation locates in the acceptor splice site of exon 2 and is predicted to cause failure of normal splicing of HOXD13. The foot abnormality in this family is similar to that described in two families by Goodman et al. [1998: Am. J. Hum. Genet. 63: 992-1000] in which different deletions of HOXD13 were reported. These findings together lend support to a distinct phenotype resulting from haploinsufficiency of HOXD13.
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Shih-hsin
authors.initials: SH
authors.lastname: Kan
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.forename: Henk
authors.initials: H
authors.lastname: Giele
authors.forename: Andrew O M
authors.initials: AO
authors.lastname: Wilkie
mesh_terms: D001483:Base Sequence / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005532:Foot Deformities, Congenital / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D022821:RNA Splice Sites / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*; D013576:Syndactyly / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D022821:RNA Splice Sites; D014157:Transcription Factors