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Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282X

Arq. Neuro-Psiquiatr. vol.55 no.2 São Paulo June 1997 

Clinical-neurologic, cytogenetic and molecular aspects of the Prader-Willi and Angelman Syndromes


Aspectos clínico-neurológicos, citogenéticos e moleculares das síndromes de Prader-Willi e Angelman



João M. de Pina-NetoI; Victor Evangelista F. FerrazI; Greice Andreotti de MolfettaI; Jess BuxtonII; Sarah RichardsII; Sue MalcolmII

IDepartment of Genetics, Medical School of Riberião Preto - University of São Paulo (FMRP-USP)
IIMolecuIar Genetics Unit, Institute of Child Health, University of London




The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are human neurogenetic disorders involving the imprinting mechanism, at the 15q11-13 chromosome region. The predominant genetic defects in PW are 15q 11-13 deletions of paternal origin and maternal chromosome 15 uniparental disomy. In contrast, maternal deletions and paternal chromosome 15 uniparental disomy are associated with a different neurogenetic disorder, the AS. In both disorders, these mutations are associated with parent-of-origin specific methylation at several 15q 11-13 loci. We studied 5 patients suspect of PWS and 4 patients suspect of AS who were referred to the Medical Genetics Unit at the University Hospital of Medical School from Ribeirão Preto. Our objective was to establish the correct clinical and etiological diagnosis in these cases. We used conventional cytogenetics, methylation analysis with the probe KB 17 (CpG island of the SNRPN gene) by Southern blotting after digestion with the Xba I and Not I restriction enzymes. We studied in patients and their parents the segregation of the (CA)n repeats polymorphisms by PCR, using the primers 196 and IR4-3R. All the patients had normal conventional cytogenetical analysis. We confirmed 3 cases of PWS: one by de novo deletion, one by maternal chromosome 15 uniparental disomy and one case with no defined cause determined by the used primers. We confirmed 2 cases of AS, caused by de novo deletion at the 15q 11-13 region, and one case with normal molecular analysis but with strong clinical characteristics.

Key words: medical genetics, mental retardation, Prader-Willi syndrome, Angelman syndrome, molecular genetics, PCR (polymerase chan reaction), Southern blot.


A síndrome de Prader-Willi (SPW) e a síndrome de Angelman (SA) são doenças neurogenéticas consideradas como exemplos do fenômeno de imprinting em seres humanos, estando relacionadas com alterações envolvendo a região cromossômica 15q11-13. As alterações genéticas predominantes na SPW são deleções na região 15q 11-13 de origem paterna e dissomia uniparental materna. Na SA encontra-se deleções na região 15q 11-13 materna e dissomia uniparental paterna. Estudamos 5 pacientes com suspeita clínica de SPW e 4 pacientes com suspeita clínica de SA atendidos no Setor de Genética Médica do Hospital Universitário da FMRP-USP, com o objetivo de estabelecer o diagnóstico clínico e etiológico de certeza nessa amostra. Para isso utilizamos citogenética convencional, estudo de metilação por Southern blotting utilizando a sonda KB 17 (ilha CpG do gene SNRPN) após digestão com as enzimas de restrição Xba I e Not I e análise de polimorfismos de repetição de CA por PCR, usando os primers 196 e IR4-3R. Dos 9 pacientes avaliados, todos tiveram avaliação citogenética convencional normal. Foram confirmados a nível molecular, 1 caso de SPW por deleção nova, 1 caso de SPW por dissomia uniparental materna e 1 caso de SPW em que a causa genética não pode ser esclarecida pela análise de polimorfismo com os primers usados. Foram confirmados a nível molecular 2 casos de SA, ambos por deleção nova na região 15q 11-13, e 1 caso de SA cuja clínica é extremamente sugestiva mas no qual não foi evidenciada alteração em qualquer dos exames moleculares utilizados.

Palavras-chave: genética médica; deficiência mental; síndrome de Prader-Willi; síndrome de Angelman; genética molecular; PCR (polymerase chain reaction); Southern blot.



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Aceite: 17-fevereiro-1997.



Dr. João Monteiro de Pina Neto - Departamento de Genética, Faculdade de Medicina de Ribeirão Preto USP - Av. Bandeirantes 3900 - 14049-900 Ribeirão Preto SP - Brasil.

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