Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome

Autor: Solange Aliaga Vera, Emma Baker, Víctor Faundes, Michael Field, Matthew F. Hunter, Minh Bui, Bianca Curotto, Isabel Salas, Ling Ling, Jonathan Cohen, Angelica M. Alliende, Lorena Santa María, Justine Elliott, Marta Arpone, Claudine Kraan, Alexandra Ure, Cesar Trigo, David J. Amor, David E. Godler, Carolyn Rogers, David Francis, Paulina Morales, Lesley Bretherton
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Adult
Male
Adolescent
Cognitive Neuroscience
Behavioral Symptoms
Intellectual functioning
Pathology and Forensic Medicine
lcsh:RC321-571
Cohort Studies
03 medical and health sciences
Fragile X Mental Retardation Protein
Young Adult
0302 clinical medicine
Borderline intellectual functioning
Sex Factors
Intellectual Disability
Intellectual disability
medicine
Humans
0501 psychology and cognitive sciences
Behaviour
Autism spectrum disorder
10. No inequality
Child
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Intelligence quotient
business.industry
Mosaicism
Research
05 social sciences
Neuropsychology
Infant
medicine.disease
FMR1
Fragile X syndrome
Phenotype
Child
Preschool
Pediatrics
Perinatology and Child Health
Mutation
Autism
Female
Neurology (clinical)
business
030217 neurology & neurosurgery
050104 developmental & child psychology
Clinical psychology
Zdroj: Journal of Neurodevelopmental Disorders, Vol 11, Iss 1, Pp 1-15 (2019)
Journal of Neurodevelopmental Disorders
ISSN: 1866-1955
1866-1947
Popis: BackgroundFragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with a CGG expansion, termed full mutation (FM: CGG ≥ 200), increased DNA methylation of theFMR1promoter and silencing of the gene. Mosaicism for presence of cells with either methylated FM or smaller unmethylated pre-mutation (PM: CGG 55–199) alleles in the same individual have been associated with better cognitive functioning. This study compares age- and sex-matched FM-only and PM/FM mosaic individuals on intellectual functioning, ASD features and maladaptive behaviours.MethodsThis study comprised a large international cohort of 126 male and female participants with FXS (aged 1.15 to 43.17 years) separated into FM-only and PM/FM mosaic groups (90 males, 77.8% FM-only; 36 females, 77.8% FM-only). Intellectual functioning was assessed with age appropriate developmental or intelligence tests. The Autism Diagnostic Observation Schedule-2nd Edition was used to examine ASD features while the Aberrant Behavior Checklist-Community assessed maladaptive behaviours.ResultsComparing males and females (FM-only + PM/FM mosaic), males had poorer intellectual functioning on all domains (p< 0.0001). Although females had less ASD features and less parent-reported maladaptive behaviours, these differences were no longer significant after controlling for intellectual functioning. Participants with PM/FM mosaicism, regardless of sex, presented with better intellectual functioning and less maladaptive behaviours compared with their age- and sex-matched FM-only counterparts (p< 0.05). ASD features were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning.ConclusionsMales with FXS had significantly lower intellectual functioning than females with FXS. However, there were no significant differences in ASD features and maladaptive behaviours, after controlling for intellectual functioning, independent of the presence or absence of mosaicism. This suggests that interventions that primarily target cognitive abilities may in turn reduce the severity of maladaptive behaviours including ASD features in FXS.
Databáze: OpenAIRE
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