title: Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes.
abstract: During the last few years, several studies have reported an excess of intermediate FMR1 alleles in patients with cognitive and/or behavioural phenotypes. Here, we report the frequency of intermediate alleles (IAs) in three pathologies, intellectual disabilities (IDs), attention-deficit/hyperactivity disorder and autism, from different Spanish regions. We found 142 IAs among 9015 patients with ID (1.6%), 4 among the 415 ADHD patients (0.96%) and 4 among the 300 autistic patients (1.3%), similar to the frequency reported in our control population. No evidence was found of an excess of IA at the FRAXA locus in any of the study populations, although geographical variability was detected. Moreover, the analysis of 100 transmissions of IAs showed that 95% of these alleles were stable. Only 3% expanded within the same range and 2% expanded to a full mutation in two generations. No evidence of an association between IAs and behavioural or cognitive phenotypes was found, suggesting that IAs are not clearly implicated in these pathologies.
authors.affiliation: CIBER de Enfermedades Raras and Biochemistry and Molecular Genetics Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Madrigal
authors.forename: Mar
authors.initials: M
authors.lastname: Xunclà
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Tejada
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez
authors.forename: Isabel
authors.initials: I
authors.lastname: Fernández-Carvajal
authors.forename: Luís Alberto
authors.initials: LA
authors.lastname: Pérez-Jurado
authors.forename: Laia
authors.initials: L
authors.lastname: Rodriguez-Revenga
authors.forename: Montserrat
authors.initials: M
authors.lastname: Milà
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology; D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology; D005787:Gene Frequency; D006801:Humans; D008297:Male; D013030:Spain; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human