Chromosome rearrangements in Cornelia de Lange syndrome (CdLS): Report of a der(3)t(3;12)(p25.3;p13.3) in two half sibs with features of CdLS and review of reported CdLS cases with chromosome rearrangements

Authors

  • Cheryl DeScipio,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, School of Medicine, and The University of Pennsylvania, Philadelphia, Pennsylvania
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  • Maninder Kaur,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, School of Medicine, and The University of Pennsylvania, Philadelphia, Pennsylvania
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  • Dinah Yaeger,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, School of Medicine, and The University of Pennsylvania, Philadelphia, Pennsylvania
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  • Jeffrey W. Innis,

    1. Division of Pediatric Genetics, University of Michigan, Ann Arbor, Michigan
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  • Nancy B. Spinner,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, School of Medicine, and The University of Pennsylvania, Philadelphia, Pennsylvania
    2. Division of Clinical Labs, The Children's Hospital of Philadelphia, School of Medicine, and The University of Pennsylvania, Philadelphia, Pennsylvania
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  • Laird G. Jackson,

    1. Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, Pennsylvania
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  • Ian D. Krantz

    Corresponding author
    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, School of Medicine, and The University of Pennsylvania, Philadelphia, Pennsylvania
    • Division of Human Genetics and Molecular Biology, 1002 Abramson Research Building, The Children's Hospital of Philadelphia, 34th Street and Civic Center Blvd. Philadelphia, Pennsylvania 19104.
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Abstract

Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited disorder characterized by multisystem involvement, cognitive delay, limb defects, and characteristic facial features. Recently, mutations in NIPBL have been found in ∼50% of individuals with CdLS. Numerous chromosomal rearrangements have been reported in individuals with CdLS. These rearrangements may be causative of a CdLS phenotype, result in a phenocopy, or be unrelated to the observed phenotype. We describe two half siblings with a der(3)t(3;12)(p25.3;p13.3) chromosomal rearrangement, clinical features resembling CdLS, and phenotypic overlap with the del(3)(p25) phenotype. Region-specific BAC probes were used to fine-map the breakpoint region by fluorescence in situ hybridization (FISH). FISH analysis places the chromosome 3 breakpoint distal to RP11-115G3 on 3p25.3; the chromosome 12 breakpoint is distal to BAC RP11-88D16 on 12p13.3. A review of published cases of terminal 3p deletions and terminal 12p duplications indicates that the findings in these siblings are consistent with the del(3)(p25) phenotype. Given the phenotypic overlap with CdLS, we have reviewed the reported cases of chromosomal rearrangements involved in CdLS to better elucidate other potential loci that could harbor additional CdLS genes. Additionally, to identify chromosome rearrangements, genome-wide array comparative genomic hybridization (CGH) was performed on eight individuals with typical CdLS and without identifiable deletion or mutation of NIPBL. No pathologic rearrangements were identified. © 2005 Wiley-Liss, Inc.

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