Somatic/gonadal mosaicism in a syndromic form of ectrodactyly, including eye abnormalities, documented through array-based comparative genomic hybridization

Authors

  • Aguinaldo Bonalumi Filho,

    1. Group for Advanced Molecular Investigation (NIMA), Graduate Program in Health Sciences (PPGCS), Center for Biological and Health Sciences (CCBS), Pontifícia Universidade Católica do Parana (PUCPR), Curitiba, PR, Brazil
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  • Josiane Souza,

    1. Group for Advanced Molecular Investigation (NIMA), Graduate Program in Health Sciences (PPGCS), Center for Biological and Health Sciences (CCBS), Pontifícia Universidade Católica do Parana (PUCPR), Curitiba, PR, Brazil
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  • Fábio Rueda Faucz,

    1. Group for Advanced Molecular Investigation (NIMA), Graduate Program in Health Sciences (PPGCS), Center for Biological and Health Sciences (CCBS), Pontifícia Universidade Católica do Parana (PUCPR), Curitiba, PR, Brazil
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  • Vanessa Santos Sotomaior,

    1. Group for Advanced Molecular Investigation (NIMA), Graduate Program in Health Sciences (PPGCS), Center for Biological and Health Sciences (CCBS), Pontifícia Universidade Católica do Parana (PUCPR), Curitiba, PR, Brazil
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  • Barbara Dupont,

    1. Greenwood Genetic Center, Greenwood, South Carolina
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  • Frank Bartel,

    1. Greenwood Genetic Center, Greenwood, South Carolina
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  • Reycel Rodriguez,

    1. Greenwood Genetic Center, Greenwood, South Carolina
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  • Charles E. Schwartz,

    1. Greenwood Genetic Center, Greenwood, South Carolina
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  • Cindy Skinner,

    1. Greenwood Genetic Center, Greenwood, South Carolina
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  • Sarah Alliman,

    1. Signature Genomics, Spokane, Washington
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  • Salmo Raskin

    Corresponding author
    1. Group for Advanced Molecular Investigation (NIMA), Graduate Program in Health Sciences (PPGCS), Center for Biological and Health Sciences (CCBS), Pontifícia Universidade Católica do Parana (PUCPR), Curitiba, PR, Brazil
    2. Genetika, Centro de Aconselhamento e Laboratório de Genética, Curitiba, Brazil
    • Genetika, Centro de Aconselhamento e Laboratório de Genética, Rua Saldanha Marinho 1782, 80730-180 Curitiba, Brazil.
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  • How to Cite this Article: Filho AB, Souza J, Faucz FR, Sotomaior VS, Dupont B, Bartel F, Rodriguez R, Schwartz CE, Skinner C, Alliman S, Raskin S. 2011. Somatic/gonadal mosaicism in a syndromic form of ectrodactyly, including eye abnormalities, documented through array-based comparative genomic hybridization. Am J Med Genet Part A 155:1152–1156.

Abstract

Split hand/foot malformation (SHFM) is characterized by underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits. SHFM is a heterogeneous condition caused by abnormalities at one of multiple loci, including SHFM1 (SHFM1 at 7q21–q22), SHFM2 (Xq26), SHFM3 (FBXW4/DACTYLIN at 10q24), SHFM4 (TP63 at 3q27), and SHFM5 (DLX1 and DLX 2 at 2q31). SHFM3 is unique in that it is caused by submicroscopic tandem chromosome duplications of FBXW4/DACTYLIN. In order to show that array-based comparative genomic hybridization should be considered an essential aspect of the genetic analysis of patients with SHFM, we report on a family with two brothers who have ectrodactyly. Interestingly, both also have ocular abnormalities. Their sister and both parents are healthy. DNA of all five family members was analyzed using oligonucleotide-based DNA microarray and quantitative PCR. The two affected brothers were found to have a small duplication of approximately 539 kb at 10q24.32. The patients' sister and father do not have the microduplication, but qPCR showed that mother's DNA carries the duplication in 20% of blood lymphocytes. In this family, two children were affected with ectrodactyly having a duplication over the SHFM3 locus. The mother, who shows no clinical features of ectrodacytyly, is a mosaic for the same duplication. Therefore, we demonstrate that somatic/gonadal mosaicism is a mechanism that gives rise to SHFM. We also suggest that ocular abnormalities may be part of the clinical description of SHFM3. © 2011 Wiley-Liss, Inc.

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