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Obesity with associated developmental delay and/or learning disability in patients exhibiting additional features: Report of novel pathogenic copy number variants

Authors

  • Carla Sustek D'Angelo,

    Corresponding author
    1. Human Genome and Stem Cell Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
    • Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Rua do Matao, 277, room 204/209, 05508-090, Sao Paulo, SP, Brazil.
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  • Ilana Kohl,

    1. Human Genome and Stem Cell Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
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  • Monica Castro Varela,

    1. Human Genome and Stem Cell Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
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  • Cláudia Irene Emílio de Castro,

    1. Human Genome and Stem Cell Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
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  • Chong Ae Kim,

    1. Genetics Unit, Department of Pediatrics, Children Institute, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
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  • Débora Romeo Bertola,

    1. Genetics Unit, Department of Pediatrics, Children Institute, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
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  • Charles Marques Lourenço,

    1. Neurogenetics Unit, Department of Medical Genetics, School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil
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  • Ana Beatriz Alvarez Perez,

    1. Department of Morphology, Medical Genetics Center, Federal University of Sao Paulo, Sao Paulo, Brazil
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  • Celia Priszkulnik Koiffmann

    1. Human Genome and Stem Cell Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
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  • Conflicts of interest: None.

  • How to Cite this Article: D'Angelo CS, Kohl I, Varela MC, de Castro CIE, Kim CA, Bertola DR, Lourenço CM, Perez ABA, Koiffmann CP. 2013. Obesity with associated developmental delay and/or learning disability in patients exhibiting additional features: Report of novel pathogenic copy number variants. Am J Med Genet Part A 161A: 479–486.

Abstract

Obesity is a major threat to public health worldwide, and there is now mounting evidence favoring a role for the central nervous system (CNS) in weight control. A causal relationship has been recognized in both monogenic (e.g., BDNF, TRKB, and SIM1 deficiencies) and syndromic forms of obesity [e.g., Prader–Willi syndrome (PWS)]. Syndromic obesity arising from chromosomal abnormalities, that typically also affect learning and development, are often associated with congenital malformations and behavioral characteristics. We report on nine unrelated patients with a diagnosis of learning disability and/or developmental delay (DD) in addition to obesity that were found to have copy number variants (CNVs) by single nucleotide polymorphism array-based analysis. Each patient also had a distinct and complex phenotype, and most had hypotonia and other neuroendocrine issues, such as hyperphagia and hypogonadism. Molecular and clinical characterization of these patients enabled us to determine with confidence that the CNVs we observed were pathogenic or likely to be pathogenic. Overall, the CNVs reported here encompassed a candidate gene or region (e.g., SIM1) that has been reported in patients associating obesity and DD and/or intellectual disability (ID) and novel candidate genes and regions. © 2013 Wiley Periodicals, Inc.

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