Journal of Intellectual Disability - Diagnosis and Treatment

126-137

Authors: Silvia Russo, Ester Mainini, Chiara Luoni, Francesca Cogliati, Valentina Giorgini, Maria Teresa Bonati, Francesca Forzano, Cristiano Termine, Alessandra Murgia, Mara Patrini, Antonella Fabretto, Skabar Aldo, Elena Freri, Vanna Pecile, Lidia Larizza

Angelman Syndrome (AS) is due to the loss of function of the single UBE3A gene, mapping to chromosome 15q11-q13 and encoding the E6AP ubiquitin ligase. Expression of UBE3A is subject to genomic imprinting which is restricted to the brain, where only the maternal allele is transcribed. AS pathogenetic mechanisms include deletion of the maternal 15q11-13 chromosomal region, chromosome 15 paternal uniparental disomy (UPD), Imprinting Defects (ImpD) leading to silencing of the maternal allele and intragenic mutations of the maternal UBE3A allele. From our AS cohort we sorted out for detailed clinical-molecular characterization six mosaic cases, five with ImpD epimutations and one with patUPD15. This latter case referred for intellectual disability and fortuitously solved by SNP array, is, to our knowledge, the unique patient reported with mosaic patUPD of this imprinted region. Somatic epimutation mosaicism represents a challenge for both clinical and molecular diagnostics. The described patients, referred to our center either for uncertain AS or simply for intellectual disability, could be molecularly characterized by applying a multi-method approach including Methylation-Sensitive PCR and MS-MLPA without a strict cut off. The percentage of normal cells detected ranged up to 40%. We confirm the mild phenotype reported in mosaic AS ImpD and provide a detailed analysis of IQ. Mild mental retardation, with significant difficulties in language expression, but only mildly impaired performance skills, together with pathognomonic EEG, is a cue not to overlook in mosaic AS patients. Mosaic epimutations should be searched also in patients with minor AS features and presenting only with intellectual disability.

147-153

Authors: Aneta Rita Borkowska

The study was designed to investigate selected aspects of language and communicative functions as well as verbal fluency in children with HFA. The study group comprised 51 children, aged 10-12, including 23 subjects diagnosed with High-Functioning Autism, with normal IQ and able to communicate verbally, as well as a group of 28 controls. The applied tools included RHLB-PL Battery, a verbal fluency task and WISC-R Vocabulary subtest. The findings show significantly varied profiles of the investigated functions in the group of children with HFA. In comparison with their peers, they have greater difficulties drawing logical conclusions from stories. They find it difficult to grasp humour conveyed by linguistic expression and by metaphors, presented with the use of both linguistic materials and drawings. They have lower capacitates for understanding prosodic (emotional and language) aspects of utterances addressed to them. It has been established that they are able to correctly understand isolated words and recognize their designates despite the present distractors. No generalized deficits have been found in the subjects' verbal fluency. In comparison to the controls, the children with HFA generated similar number of words matching the phonemic criterion. Furthermore, their performance showed no perseverations, and comparably frequent clustering and switching. Lexicon matching the semantic criterion was more difficult to access for the children with HFA than for the controls. Children with HFA had difficulties in defining familiar words.