An atypical 0.73 MB microduplication of 22q11.21 and a novel SALL4 missense mutation associated with thumb agenesis and radioulnar synostosis

Adam Diehl, Weiyi Mu, Denise Batista, Meral Gunay-Aygun

Research output: Contribution to journalArticle

Abstract

We describe a 0.73Mb duplication of chromosome 22q11.21 between LCR-B and LCR-D and a missense mutation in a conserved C2H2 zinc finger domain of SALL4 in a cognitively normal patient with multiple skeletal anomalies including radioulnar synostosis, thumb aplasia, butterfly vertebrae, rib abnormalities, and hypoplasia of the humeral and femoral epiphyses. 22q11.21 is a common site for microdeletions and their reciprocal microduplications as a result of non-allelic homologous recombination between its multiple low copy repeat regions (LCR). DiGeorge /Velocardiofacial syndrome (DG/VCFS) is classically caused by a 3Mb deletion between LCR-A and LCR-D or a 1.5Mb deletion between LCR-A and LCR-B. The reciprocal syndrome to DG/VCFS is the recently described 22q11.2 microduplication, which usually presents with the typical 3Mb or 1.5Mb duplication. Numerous atypical deletions and duplications have been reported between other LCRs. Typically, SALL4-related Duane-radial ray syndrome is caused by deletions or nonsense mutations; the only missense SALL4 mutation described prior was thought to result in gain of function and produced cranial midline defects. The skeletal anomalies presented in this report have not been previously described in association with 22q11.2 microduplication nor SALL4 mutations.

Original languageEnglish (US)
Pages (from-to)1644-1649
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume167
Issue number7
DOIs
StatePublished - Jul 1 2015

Fingerprint

Genomic Segmental Duplications
Synostosis
Thumb
Missense Mutation
DiGeorge Syndrome
Duane Retraction Syndrome
Chromosome Duplication
Butterflies
Epiphyses
Nonsense Codon
Sequence Deletion
Homologous Recombination
Zinc Fingers
Ribs
Thigh
Spine
Mutation

Keywords

  • Chromosome 22q11.21 microduplication syndrome
  • Radioulnar synostosis
  • SALL4
  • Thumb agenesis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

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title = "An atypical 0.73 MB microduplication of 22q11.21 and a novel SALL4 missense mutation associated with thumb agenesis and radioulnar synostosis",
abstract = "We describe a 0.73Mb duplication of chromosome 22q11.21 between LCR-B and LCR-D and a missense mutation in a conserved C2H2 zinc finger domain of SALL4 in a cognitively normal patient with multiple skeletal anomalies including radioulnar synostosis, thumb aplasia, butterfly vertebrae, rib abnormalities, and hypoplasia of the humeral and femoral epiphyses. 22q11.21 is a common site for microdeletions and their reciprocal microduplications as a result of non-allelic homologous recombination between its multiple low copy repeat regions (LCR). DiGeorge /Velocardiofacial syndrome (DG/VCFS) is classically caused by a 3Mb deletion between LCR-A and LCR-D or a 1.5Mb deletion between LCR-A and LCR-B. The reciprocal syndrome to DG/VCFS is the recently described 22q11.2 microduplication, which usually presents with the typical 3Mb or 1.5Mb duplication. Numerous atypical deletions and duplications have been reported between other LCRs. Typically, SALL4-related Duane-radial ray syndrome is caused by deletions or nonsense mutations; the only missense SALL4 mutation described prior was thought to result in gain of function and produced cranial midline defects. The skeletal anomalies presented in this report have not been previously described in association with 22q11.2 microduplication nor SALL4 mutations.",
keywords = "Chromosome 22q11.21 microduplication syndrome, Radioulnar synostosis, SALL4, Thumb agenesis",
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AU - Mu,Weiyi

AU - Batista,Denise

AU - Gunay-Aygun,Meral

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N2 - We describe a 0.73Mb duplication of chromosome 22q11.21 between LCR-B and LCR-D and a missense mutation in a conserved C2H2 zinc finger domain of SALL4 in a cognitively normal patient with multiple skeletal anomalies including radioulnar synostosis, thumb aplasia, butterfly vertebrae, rib abnormalities, and hypoplasia of the humeral and femoral epiphyses. 22q11.21 is a common site for microdeletions and their reciprocal microduplications as a result of non-allelic homologous recombination between its multiple low copy repeat regions (LCR). DiGeorge /Velocardiofacial syndrome (DG/VCFS) is classically caused by a 3Mb deletion between LCR-A and LCR-D or a 1.5Mb deletion between LCR-A and LCR-B. The reciprocal syndrome to DG/VCFS is the recently described 22q11.2 microduplication, which usually presents with the typical 3Mb or 1.5Mb duplication. Numerous atypical deletions and duplications have been reported between other LCRs. Typically, SALL4-related Duane-radial ray syndrome is caused by deletions or nonsense mutations; the only missense SALL4 mutation described prior was thought to result in gain of function and produced cranial midline defects. The skeletal anomalies presented in this report have not been previously described in association with 22q11.2 microduplication nor SALL4 mutations.

AB - We describe a 0.73Mb duplication of chromosome 22q11.21 between LCR-B and LCR-D and a missense mutation in a conserved C2H2 zinc finger domain of SALL4 in a cognitively normal patient with multiple skeletal anomalies including radioulnar synostosis, thumb aplasia, butterfly vertebrae, rib abnormalities, and hypoplasia of the humeral and femoral epiphyses. 22q11.21 is a common site for microdeletions and their reciprocal microduplications as a result of non-allelic homologous recombination between its multiple low copy repeat regions (LCR). DiGeorge /Velocardiofacial syndrome (DG/VCFS) is classically caused by a 3Mb deletion between LCR-A and LCR-D or a 1.5Mb deletion between LCR-A and LCR-B. The reciprocal syndrome to DG/VCFS is the recently described 22q11.2 microduplication, which usually presents with the typical 3Mb or 1.5Mb duplication. Numerous atypical deletions and duplications have been reported between other LCRs. Typically, SALL4-related Duane-radial ray syndrome is caused by deletions or nonsense mutations; the only missense SALL4 mutation described prior was thought to result in gain of function and produced cranial midline defects. The skeletal anomalies presented in this report have not been previously described in association with 22q11.2 microduplication nor SALL4 mutations.

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