Reference:
RES-145-28n.a.003
Abstract:
We aimed to improve the understanding of genotypeﾖphenotype correlations in Rett syndrome (RS) by adopting a novel approach to categorising phenotypic dimensions ﾖ separating typicality of presentation, outcome severity and age of onset ﾖ and by classifyingﾠMECP2ﾠmutations strictly by predicted functional attributes.ﾠMECP2ﾠmutation screening results were available on 190 patients with a clinical diagnosis of RS (140 cases with classic RS, 50 with atypical RS). 135 cases had identified mutations. Of the 140 patients, 116 with classic RS (82.9%) had an identified mutation compared with 19 of 50 patients (38%) with an atypical presentation. Cases with early onset of regression and seizures, and those with clinical features that might indicate alternative aetiologies, were less likely to have mutations. Individuals with late truncating mutations had a less typical presentation than cases with missense and early truncating mutations, presumably reflecting greater residual function of MECP2 protein. Individuals with early truncating mutations had a more severe outcome than cases with missense and late truncating mutations. These findings held when restricting the analysis to cases over 15 years of age and classic cases only. Previous findings of variation in severity among the common mutations were confirmed. The approach to phenotypic and genotypic classification adopted here allowed us to identify genotypeﾖphenotype associations in RS that may aid our understanding of pathogenesis and also contribute to clinical knowledge on the impact of different types of mutations.
PROJECT DETAILS
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Country of research: United Kingdom
Counry of funding source: United Kingdom
Funding organization: Economic and Social Research Council Shaping Society
Financing: NATIONAL FUNDINGS – 0 €