title: Complex genetics of radial ray deficiencies: screening of a cohort of 54 patients.
abstract: OBJECTIVE
  Radial ray deficiencies are characterized by unilateral or bilateral absence of varying portions of the radius and thumb. Both isolated and syndromic forms have been described, and although for some of the syndromes the causal gene has been identified, many patients remain without a genetic diagnosis.
  
  
  METHODS
  In this study, a cohort of 54 patients with radial ray deficiencies was screened for genomic aberrations by molecular karyotyping.
  
  
  RESULTS
  In 8 of 54 cases, an aberration was detected. Two unrelated patients inherited a 1q21.1 microduplication from a healthy parent, whereas in a third patient, a 16p13.11 microduplication was identified. Two other interesting microdeletions were detected: a 10q24.3 deletion at the split hand-foot malformation (SHFM3) locus and a 7p22.1 deletion including the RAC1 gene.
  
  
  CONCLUSIONS
  The finding of these microduplications may just be coincidental or, alternatively, they may illustrate the broad phenotypic spectrum of these microduplications. Duplications in the 10q24.3 region result in split hand-foot malformations, and our observation indicates that deletions may cause radial ray defects. Finally, a candidate gene for radial ray deficiencies was detected in the 7p22.1 deletion. RAC1 plays an important role in the canonical Wnt pathway and conditional RAC1 knockout mice exhibit truncated-limb defects.
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vergult
authors.forename: A Jeannette M
authors.initials: AJ
authors.lastname: Hoogeboom
authors.forename: Emilia K
authors.initials: EK
authors.lastname: Bijlsma
authors.forename: Tom
authors.initials: T
authors.lastname: Sante
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Bram
authors.initials: B
authors.lastname: De Wilde
authors.forename: Marjolijn
authors.initials: M
authors.lastname: Jongmans
authors.forename: Christian
authors.initials: C
authors.lastname: Thiel
authors.forename: Joke B G M
authors.initials: JB
authors.lastname: Verheij
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez-Aytes
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Esch
authors.forename: Alma
authors.initials: A
authors.lastname: Kuechler
authors.forename: Daniela Q C M
authors.initials: DQ
authors.lastname: Barge-Schaapveld
authors.forename: Yves
authors.initials: Y
authors.lastname: Sznajer
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.forename: Björn
authors.initials: B
authors.lastname: Menten
mesh_terms: D058674:Chromosome Duplication; D002879:Chromosomes, Human, Pair 10; D002897:Chromosomes, Human, Pair 7; D055028:Comparative Genomic Hybridization; D044783:F-Box Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D011859:Radiography; D038062:Upper Extremity Deformities, Congenital / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D020830:rac1 GTP-Binding Protein / Q000235:genetics
chemical_list: D044783:F-Box Proteins; C120449:FBXW4 protein, human; D020830:rac1 GTP-Binding Protein