title: Obesity with associated developmental delay and/or learning disability in patients exhibiting additional features: report of novel pathogenic copy number variants.
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.
authors: Human Genome and Stem Cell Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil. cdangelo@ib.usp.br
authors: Carla Sustek
authors: CS
authors: D'Angelo
authors: Ilana
authors: I
authors: Kohl
authors: Monica Castro
authors: MC
authors: Varela
authors: Cláudia Irene Emílio
authors: CI
authors: de Castro
authors: Chong Ae
authors: CA
authors: Kim
authors: Débora Romeo
authors: DR
authors: Bertola
authors: Charles Marques
authors: CM
authors: Lourenço
authors: Ana Beatriz Alvarez
authors: AB
authors: Perez
authors: Celia Priszkulnik
authors: CP
authors: Koiffmann
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007859:Learning Disabilities / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D025202:Molecular Diagnostic Techniques; D009765:Obesity / Q000175:diagnosis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide