Extending the Phenotype of Monosomy 1p36 Syndrome and Mapping of a Critical Region for Obesity and Hyperphagia

Autor(es)

D'Angelo, Carla S. ^[1] ; Kohl, Ilana ^[1] ; Varela, Monica Castro ^[1] ; de Castro, Claudia I. E. ^[1] ; Kim, Chong A. ^[2] ; Bertola, Debora R. ^[2] ; Lourenco, Charles M. ^[3] ; Koiffmann, Celia P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Evolutionary Biol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Pediat, Genet Unit, Children Inst, Sch Med, BR-05508900 Sao Paulo - Brazil

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

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF MEDICAL GENETICS PART A; v. 152A, n. 1, p. 102-110, JAN 2010.
• Citações Web of Science: 20

Resumo

Rearrangements of 1p36 are the most frequently detected abnormalities in diagnostic testing for chromosomal cryptic imbalances and include variably sized simple terminal deletions, derivative chromosomes, interstitial deletions, and complex rearrangements. These rearrangements result in the specific pattern of malformation and neurodevelopmental disabilities that characterizes monosomy 1p36 syndrome. Thus far, no individual gene within this region has been conclusively determined to be causative of any component of the phenotype. Nor is it known if the rearrangements convey phenotypes via a haploinsufficiency mechanism or through a position effect. We have used multiplex ligation-dependent probe amplification to screen for deletions of 1p36 in a group of 154 hyperphagic and overweight/obese, PWS negative individuals, and in a separate group of 83 patients initially sent to investigate a variety of other conditions. The strategy allowed the identification and delineation of rearrangements in nine subjects with a wide spectrum of clinical presentations. Our work reinforces the association of monosomy 1p36 and obesity and hyperphagia, and further suggests that these features may be associated with non-classical manifestations of this disorder in addition to a submicroscopic deletion of similar to 2-3 Mb in size. Multiplex ligation probe amplification using the monosomy 1p36 syndrome-specific kit coupled to the subtelomeric kit is an effective approach to identify and delineate rearrangements at 1p36. (C) 2009 Wiley-Liss, Inc. (AU)

• Processo FAPESP: 04/10380-6 - Sindrome da monossomia 1p36: investigacao de delecoes em 1p36 e de suas correlacoes genotipo-fenotipo.
• Beneficiário: Carla Sustek D'Angelo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• 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