Publication
Study of FRAXE-MR in intellectually disabled individuals referred for Fragile-X Syndrome testing in Portugal
| dc.contributor.author | Jorge, Paula | |
| dc.contributor.author | Marques, Isabel | |
| dc.contributor.author | Gonçalves, Rui | |
| dc.contributor.author | Gonçalves-Rocha, Miguel | |
| dc.contributor.author | Santos, Rosário | |
| dc.date.accessioned | 2013-02-07T15:27:31Z | |
| dc.date.available | 2013-02-07T15:27:31Z | |
| dc.date.issued | 2012-06-23 | |
| dc.description | Abstrat publicado em: European Journal of Human Genetics jun 2012;20(Suppl1):308 (P12.097). Disponível em: https://www.eshg.org/fileadmin/www.eshg.org/conferences/2012/ESHG2012Abstracts.pdf | por |
| dc.description.abstract | Among the genetic causes involved in X-linked intellectual disability (XLID), pathogenic variations in FMR1 (Fragile Mental Retardation 1), AFF2 (AF4/ FMR2 family member 2) and ARX (Aristaless Related Homeobox) genes emerge as main causes. FMR1 and AFF2 genes contain (polymorphic repetitive regions) a repeat polymorphism which is susceptible to suffer dynamic mutation, a process that may induce pathogenic expansions. FRAXEassociated mental retardation (FRAXE-MR) is mainly a non-syndromic form of XLID and is due to AFF2 gene silencing as a consequence of 5’UTR-CCG expansion or gene mutations. A CCG triplet number up to 30 repeats is consider normal, while full expansion (>200 repeats) and hypermethylation of CCG cluster results in FRAXE-MR. AFF2 variants are not frequently sought. An implementation of a cost-effective strategy (co-amplification with other ID genes) represents an improvement in molecular diagnosis with consequent gains in clinical genetic diagnosis and counseling. Herein we present results of AFF2 molecular analysis in a subpopulation of 5000 intellectually-disabled individuals with primary referral for FRAXA screening, by a novel multiplex-PCR strategy. This approach accurately detected normal to pre-mutated alleles. A pre-mutated allele with 68 CCG was identified and further characterized by Southern blot analysis in order to exclude methylation and/or repeat number mosaics, as well as PCR failure. Possible phenotype-genotype correlations based on the clinical data of one previously diagnosed family with AFF2 full expansion, the newly characterized pre-mutation carrier and one case with a new variant of the AFF2 gene will be investigated and presented. | por |
| dc.description.sponsorship | Genelink | por |
| dc.identifier.uri | http://hdl.handle.net/10400.18/1199 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Instituto Nacional de Saúde Doutor Ricardo Jorge, IP | por |
| dc.subject | Doenças Genéticas | por |
| dc.subject | FRAXE Mental Retardation | por |
| dc.subject | X-linked Intellectual Disability (XLID) | por |
| dc.subject | Dynamic Mutations | por |
| dc.subject | AFF2 gene (AF4/FMR2 family member 2) | por |
| dc.subject | Fragile-X Syndrome | por |
| dc.title | Study of FRAXE-MR in intellectually disabled individuals referred for Fragile-X Syndrome testing in Portugal | por |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Nurnberg, Germany | por |
| oaire.citation.title | European Human Genetics Conference, 23-26 June 2012 | por |
| rcaap.rights | restrictedAccess | por |
| rcaap.type | conferenceObject | por |