Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Phenotypic variability in Angelman syndrome: comparison among different deletion classes and between deletion and UPD subjects

Texto completo
Autor(es):
Varela, Monica Castro [1] ; Kok, Fernando ; Otto, Paulo Alberto ; Koiffmann, Celia Priszkulnik [4]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Universidade de São Paulo (USP). Instituto de Biociências - Brasil
[4] Universidade de São Paulo (USP). Instituto de Biociências - Brasil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: European Journal of Human Genetics; v. 12, n. 12, p. 987-992, Dec. 2004.
Área do conhecimento: Ciências Biológicas - Genética
Assunto(s):Genética médica   Síndrome de Prader-Willi   Síndrome de Angelman   Fenótipo   Doenças genéticas   Transtornos cromossômicos
Resumo

Angelman syndrome (AS) can result from either a 15q11-q13 deletion (del), paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. Here, we describe the phenotypic and behavioral variability detected in 49 patients with different classes of deletions and nine patients with UPD. Diagnosis was made by methylation pattern analysis of exon 1 of the SNRPN-SNURF gene and by microsatellite profiling of loci within and outside the 15q11-q13 region. There were no major phenotypic differences between the two main classes (BP1-BP3; BP2-BP3) of AS deletion patients, except for the absence of vocalization, more prevalent in patients with BP1-BP3 deletions, and for the age of sitting without support, which was lower in patients with BP2-BP3 deletions. Our data suggest that gene deletions (NIPA1, NIPA2, CYF1P1, GCP5) mapped to the region between breakpoints BP1 and BP2 may be involved in the severity of speech impairment, since all BP1-BP3 deletion patients showed complete absence of vocalization, while 38.1% of the BP2-BP3 deletion patients were able to pronounce syllabic sounds, with doubtful meaning. Compared to UPD patients, deletion patients presented a higher incidence of swallowing disorders (73.9% del x 22.2% UPD) and hypotonia (73.3% del x 28.57% UPD). In addition, children with UPD showed better physical growth, fewer or no seizures, a lower incidence of microcephaly, less ataxia and higher cognitive skills. As a consequence of their milder or less typical phenotype, AS may remain undiagnosed, leading to an overall underdiagnosis of the disease. (AU)

Processo FAPESP: 99/10414-8 - Caracterização dos pontos de quebra em pacientes com deleção ou duplicação do segmento 15q11 - q13 e suas consequências fenotípicas
Beneficiário:Monica Castro Varela
Linha de fomento: Bolsas no Brasil - Doutorado