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

Autor(es)

D'Angelo, Carla Sustek ^[1] ; Kohl, Ilana ^[1] ; Varela, Monica Castro ^[1] ; Emilio de Castro, Claudia Irene ^[1] ; Kim, Chong Ae ^[2] ; Bertola, Debora Romeo ^[2] ; Lourenco, Charles Marques ^[3] ; Alvarez Perez, Ana Beatriz ^[4] ; Koiffmann, Celia Priszkulnik ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Ctr, BR-05508090 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Children Inst, Genet Unit, Dept Pediat, BR-05508090 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Neurogenet Unit, Dept Med Genet, Sch Med, BR-14049 Ribeirao Preto - Brazil

^[4] Univ Fed Sao Paulo, Ctr Med Genet, Dept Morphol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF MEDICAL GENETICS PART A; v. 161A, n. 3, p. 479-486, MAR 2013.
• Citações Web of Science: 18

Resumo

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., PraderWilli 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. (c) 2013 Wiley Periodicals, Inc. (AU)

• Processo FAPESP: 98/14254-2 - Centro de Estudos do Genoma Humano
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 09/52523-1 - Obesidade sindrômica: pesquisa de genes e segmentos cromossômicos associados à obesidade, descrição de novas síndromes e da variabilidade fenotípica em síndromes reconhecidas
• Beneficiário: Carla Sustek D'Angelo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado