TY - JOUR
T1 - Complex genetics of radial ray deficiencies
T2 - Screening of a cohort of 54 patients
AU - Vergult, Sarah
AU - Hoogeboom, A. Jeannette M.
AU - Bijlsma, Emilia K.
AU - Sante, Tom
AU - Klopocki, Eva
AU - De Wilde, Bram
AU - Jongmans, Marjolijn
AU - Thiel, Christian
AU - Verheij, Joke BGM
AU - Perez-Aytes, Antonio
AU - Van Esch, Hilde
AU - Kuechler, Alma
AU - Barge-Schaapveld, Daniela QCM
AU - Sznajer, Yves
AU - Mortier, Geert
AU - Menten, Björn
PY - 2013/3
Y1 - 2013/3
N2 - Purpose: 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. Conclusion: 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.
AB - Purpose: 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. Conclusion: 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.
KW - 1q21.1 microduplication
KW - Array CGH
KW - FBXW4
KW - RAC1
KW - Radial ray deficiencies
UR - http://www.scopus.com/inward/record.url?scp=84875180187&partnerID=8YFLogxK
U2 - 10.1038/gim.2012.120
DO - 10.1038/gim.2012.120
M3 - Article
C2 - 22995989
AN - SCOPUS:84875180187
SN - 1098-3600
VL - 15
SP - 195
EP - 202
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 3
ER -