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

Autor(es)

Varela, Monica Castro ^[1] ; Kok, Fernando ; Otto, Paulo Alberto ; Koiffmann, Celia Priszkulnik ^[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

• 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 - Caracterizacao dos pontos de quebra em pacientes com delecao ou duplicacao do segmento 15q11 - q13 e suas consequencias fenotipicas.
• Beneficiário: Monica Castro Varela Rodrigues da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado