title: Absence of HOXD10 mutations in idiopathic clubfoot and sporadic vertical talus.
abstract: The genetic etiology of idiopathic clubfoot is unknown. There have been cases reported in which both clubfoot and vertical talus appears in the same family; therefore, the genes responsible for vertical talus are reasonable candidates for idiopathic clubfoot. A mutation in HOXD10 was previously identified in a family with isolated congenital vertical talus. To determine whether HOXD10 is involved in the etiology of idiopathic clubfoot, HOXD10 coding and 5' and 3' untranslated regions were resequenced in 190 patients (177 with clubfoot, 10 with sporadic vertical talus, and 3 with both clubfoot and vertical talus), and 160 ethnically matched control subjects. Rare nonsynonymous HOXD10 amino acid substitutions (Leu154Val, Asn202Lys, and Thr175Ala), likely benign variants, were all detected once in patients and control subjects. Nucleotide substitutions were also identified in HOXD10 intronic and 3' untranslated regions, but were not more frequent in cases compared to controls. To investigate the possibility that unsequenced regulatory regions play a role in this disorder, we performed linkage analysis with markers on chromosome 2q near HOXD10 in one large family. We found no evidence of linkage near the HOXD gene cluster on chromosome 2q, suggesting genes other than HOXD10 are responsible for idiopathic clubfoot.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Gurnett
authors.forename: Cassie
authors.initials: C
authors.lastname: Keppel
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bick
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dobbs
mesh_terms: D002648:Child; D002889:Chromosomes, Human, Pair 2; D003025:Clubfoot / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013628:Talus / Q000002:abnormalities*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C072064:HOXD10 protein, human