title: Duplication at chromosome 2q31.1-q31.2 in a family presenting syndactyly and nystagmus.
abstract: HOXD genes encode transcription factors involved in the antero-posterior patterning of the limb bud and in the specification of fingers. During the embryo development, HOXD genes are expressed, following a spatio-temporal colinearity that involves at least three regions, centrometric and telomeric to this cluster. Here, we describe a father and a daughter presenting a 3-4 hand bilateral syndactyly associated with a nystagmus. Array-comparative genomic hybridisation showed a 3.8 Mb duplication at 2q31.1-q31.2, comprising 27 genes including the entire HOXD cluster. We performed expression studies in lymphoblasts by reverse transcription-PCR and observed an HOXD13 and HOXD10 overexpression, whereas the HOXD12 expression was decreased. HOXD13 and HOXD10 overexpression, associated with a misregulation of at least HOXD12, may therefore induce the syndactyly. Deletions of the HOXD cluster and its regulatory sequences induce hand malformations and, particularly, finger anomalies. Recently, smaller duplications of the same region have been reported in association with a mesomelic dysplasia, type Kantaputra. We discuss the variable phenotypes associated with such 2q duplications.
authors.affiliation: Department of Molecular Biology, University Hospital, Lille, France.
authors.forename: Jamal
authors.initials: J
authors.lastname: Ghoumid
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Bernard
authors.initials: B
authors.lastname: Sablonnière
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Nathalie
authors.initials: N
authors.lastname: Philippe
authors.forename: Xavier
authors.initials: X
authors.lastname: Zanlonghi
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier-Veber
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardyn
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier-Hanu
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
mesh_terms: D000328:Adult; D002648:Child; D058674:Chromosome Duplication; D002889:Chromosomes, Human, Pair 2; D055028:Comparative Genomic Hybridization; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008297:Male; D005810:Multigene Family; D009759:Nystagmus, Pathologic / Q000000981:diagnostic imaging / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D013576:Syndactyly / Q000235:genetics*; D014314:Trisomy
chemical_list: D018398:Homeodomain Proteins