title: A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24.
abstract: Split hand-split foot malformation (SHFM) is characterized by hypoplasia/aplasia of the central digits with fusion of the remaining digits. SHFM is usually an autosomal dominant condition and at least five loci have been identified in humans. Mutation analysis of the DACTYLIN gene, suspected to be responsible for SHFM3 in chromosome 10q24, was conducted in seven SHFM patients. We screened the coding region of DACTYLIN by single-strand conformation polymorphism and sequencing, and found no point mutations. However, Southern, pulsed field gel electrophoresis and dosage analyses demonstrated a complex rearrangement associated with a approximately 0.5 Mb tandem duplication in all the patients. The distal and proximal breakpoints were within an 80 and 130 kb region, respectively. This duplicated region contained a disrupted extra copy of the DACTYLIN gene and the entire LBX1 and beta-TRCP genes, known to be involved in limb development. The possible role of these genes in the SHFM3 phenotype is discussed.
authors.affiliation: Center for Molecular Studies, J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: Xavier J
authors.initials: XJ
authors.lastname: de Mollerat
authors.forename: Fiorella
authors.initials: F
authors.lastname: Gurrieri
authors.forename: Chad T
authors.initials: CT
authors.lastname: Morgan
authors.forename: Eugenio
authors.initials: E
authors.lastname: Sangiorgi
authors.forename: David B
authors.initials: DB
authors.lastname: Everman
authors.forename: Paola
authors.initials: P
authors.lastname: Gaspari
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bamshad
authors.forename: Robert
authors.initials: R
authors.lastname: Lyle
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Blouin
authors.forename: Judith E
authors.initials: JE
authors.lastname: Allanson
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Marec
authors.forename: Melba
authors.initials: M
authors.lastname: Wilson
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Braverman
authors.forename: Uppala
authors.initials: U
authors.lastname: Radhakrishna
authors.forename: Celia
authors.initials: C
authors.lastname: Delozier-Blanchet
authors.forename: Albert
authors.initials: A
authors.lastname: Abbott
authors.forename: Vincent
authors.initials: V
authors.lastname: Elghouzzi
authors.forename: Stylianos
authors.initials: S
authors.lastname: Antonarakis
authors.forename: Roger E
authors.initials: RE
authors.lastname: Stevenson
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002461:Cell Line, Transformed; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10; D016521:Electrophoresis, Gel, Pulsed-Field; D044783:F-Box Proteins; D005530:Foot Deformities / Q000235:genetics*; D020440:Gene Duplication; D006226:Hand Deformities / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008957:Models, Genetic; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D044783:F-Box Proteins; C120449:FBXW4 protein, human; D011506:Proteins