Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

Authors

  • Yiping Shen,

    1. Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts
    2. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
    3. Harvard Medical School, Boston, Massachusetts
    4. Autism Consortium, Boston, Massachusetts
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  • Xiaoli Chen,

    1. Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts
    2. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
    3. Department of Molecular Immunology, Capital Institute of Pediatrics, Beijing, China
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  • Liwen Wang,

    1. Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, China
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  • Jin Guo,

    1. Department of Molecular Immunology, Capital Institute of Pediatrics, Beijing, China
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  • Jianliang Shen,

    1. Department of Hematology, Navy General Hospital of PLA, Beijing, China
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  • Yu An,

    1. Children's Hospital and Institutes of Biomedical Science of Fudan University, Shanghai, China
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  • Haitao Zhu,

    1. Children's Hospital and Institutes of Biomedical Science of Fudan University, Shanghai, China
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  • Yanli Zhu,

    1. Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, China
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  • Ruolei Xin,

    1. Institute of STD/AIDS Prevention and Control, Beijing Center for Disease Control and Prevention, Beijing, China
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  • Yihua Bao,

    1. Department of Molecular Immunology, Capital Institute of Pediatrics, Beijing, China
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  • James F. Gusella,

    1. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
    2. Harvard Medical School, Boston, Massachusetts
    3. Autism Consortium, Boston, Massachusetts
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  • Ting Zhang,

    Corresponding author
    1. Department of Molecular Immunology, Capital Institute of Pediatrics, Beijing, China
    • Fudan University, Shanghai China; Children's Hospital Boston and Harvard Medical School, Boston, MA.
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  • Bai-Lin Wu

    Corresponding author
    1. Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts
    2. Harvard Medical School, Boston, Massachusetts
    3. Autism Consortium, Boston, Massachusetts
    4. Children's Hospital and Institutes of Biomedical Science of Fudan University, Shanghai, China
    • Department of Molecular Immunology, Capital Institute of Pediatrics, No. 2, Yabao Road, Chaoyang District, Beijing 100020, China.
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  • How to Cite this Article: Shen Y, Chen X, Wang L, Guo J, Shen J, An Y, Zhu H, Zhu Y, Xin R, Bao Y, Gusella JF, Zhang T, Wu B-L. 2011. Intra-Family Phenotypic Heterogeneity of 16p11.2 Deletion Carriers in a Three-Generation Chinese Family. Am J Med Genet Part B 156:225–232.

  • Y. Shen and X. Chen contributed equally to this work. as co-first authors.

Abstract

The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion. © 2010 Wiley-Liss, Inc.

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