Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1265
Título: FRAXE molecular diagnosis in individuals referred for FRAXA screening
Autor: Javed, Ali
G., Ali
Caicedo, Lina
Marques, Isabel
Santos, Rosário
Jorge, Paula
Palavras-chave: Doenças Genéticas
Intellectual Disability
FRAXE
AFF2 gene
Data: 22-Nov-2012
Resumo: Introduction: FRAXE mental retardation is a form of mild to moderate intellectual disability generally associated with learning difficulties, communication deficits, attention problems, hyperactivity and autistic behavior. The folate-sensitive fragile site FRAXE (AFF2/ FMR2 gene) is ~600 kb distal to FRAXA (FMR1 gene), which is the most common cause of inherited mental retardation. Normal individuals present 4–39 copies of the polymorphic CCG repeat in AFF2, while individuals expressing the fragile site have >200 copies and the CpG island is fully methylated. Goal and methods: Reports of full expansions and pre-mutations in AFF2 are rarely documented. In this respect, it has been very difficult to determine to what extent the alleles with CCG repeats in the range of 36 to 199, have a pathogenic effect. Intellectually disabled individuals are primarily referred for FRAXA screening and individuals who are negative for FRAXA are possible candidates for FRAXE screening. In order to complement our PCR analysis with Southern blot and hybridization, we cloned a segment of the AFF2 gene that could be used as a labeled probe to determine more accurately the extent of expansion of the CCG repeats. Results and discussion: We have developed a probe to be used for Southern blot analysis that reliably detects the AFF2 CCG triple repeat amplification. We present validation data and results of AFF2 molecular analysis in a subpopulation of 5000 individuals originally referred for FRAXA screening. The presence of pre-mutated and fully expanded alleles in either gender was confirmed by Southern blot analysis, which also enabled evaluation of methylation status and exclusion of repeat number mosaics or PCR failure. We recommend the use of this probe as a method of choice for the detection of AFF2 pre-mutations, full mutations and mosaics, specifically in individuals found to be negative upon FRAXA screening.
Peer review: yes
URI: http://hdl.handle.net/10400.18/1265
Aparece nas colecções:DGH - Posters/abstracts em congressos nacionais

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