Autor(es):
Jorge, Paula 
; Marques, Isabel ; Oliveira, Bárbara ; Santos, Rosário
Data: 2011
Identificador Persistente: http://hdl.handle.net/10400.18/656
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): Doenças Genéticas; Fragile-X Syndrome
Descrição
X-linked intellectual disability (XLID) represents a common cause of monogenic mental retardation, where X-linked conditions are easily identified in affected males, who inevitably manifest a phenotype when harboring a mutant allele, due to their hemizygozity (Chiurazzi et al., 2008). Among the genetic causes involved in XLID, mutations in the Fragile Mental Retardation 1 (FMR1), AF4/FMR2 family member 2 (FMR2) and Aristaless Related Homeobox (ARX) genes emerge as important causes. FMR1 (FRAXA, locus A) and FMR2 (AFF2, FRAXE, locus E) contain polymorphic repetitive regions susceptible to suffer dynamic mutations, a process that may give rise to pathogenic expansions. The expansion to over 200 [CGG] triplets in the FMR1 gene, known as full mutation, is associated with the Fragile X Syndrome [FXS; MIM#300624], the most common form of familial severe intellectual disability (ID). In the case of the ARX gene, different mutational phenomena occur that include insertions, deletions, duplications, missense, nonsense and splice mutations. This makes it difficult to establish genotype/phenotype correlations and concomitantly clinical and molecular guidelines for the molecular analysis of ARX gene (Shoubridge et al., 2010).
With the aim to perform pre-screening in ID populations, a multiplex molecular test was developed based on basic PCR methods. The method was applied in intellectually-disabled individuals after exclusion of FMR1 full mutation, focusing on mutational hotspots within the FMR1, FMR2 and ARX genes.
