Clinical and molecular correlates in fragile X premutation females

Autor: Hiu Tung Tang, Poonnada Jiraanont, Flora Tassone, David R Hessl, Glenda M. Espinal, Andrea Schneider, Stefan R. Sweha, Nuanchan Chutabhakdikul, Reem Rafik AlOlaby, Susan M. Rivera, Paul J. Hagerman, Marisol Silva, Blythe Durbin-Johnson, Randi J Hagerman
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
congenital
hereditary
and neonatal diseases and abnormalities
Intellectual and Developmental Disabilities (IDD)
Population
Clinical Trials and Supportive Activities
Locus (genetics)
Bioinformatics
lcsh:RC346-429
03 medical and health sciences
0302 clinical medicine
Rare Diseases
Clinical Research
Executive function
Behavioral and Social Science
Genetics
Medicine
2.1 Biological and endogenous factors
Epigenetics
Aetiology
education
Psychiatric problems
lcsh:Neurology. Diseases of the nervous system
education.field_of_study
FREE2 methylation
business.industry
Depression
Premutation alleles
Cognition
FMR1
Phenotype
Brain Disorders
030104 developmental biology
Mental Health
Neurology
Sample size determination
Fragile X Syndrome
Anxiety
Original Article
medicine.symptom
business
030217 neurology & neurosurgery
Zdroj: eNeurologicalSci, Vol 7, Iss C, Pp 49-56 (2017)
eNeurologicalSci
ISSN: 2405-6502
Popis: The prevalence of the fragile X premutation (55-200 CGG repeats) among the general population is relatively high, but there remains a lack of clear understanding of the links between molecular biomarkers and clinical outcomes. In this study we investigated the correlations between molecular measures (CGG repeat size, FMR1 mRNA, FMRP expression levels, and methylation status at the promoter region and in FREE2 site) and clinical phenotypes (anxiety, obsessive compulsive symptoms, depression and executive function deficits) in 36 adult premutation female carriers and compared to 24 normal control subjects. Premutation carriers reported higher levels of obsessive compulsive symptoms, depression, and anxiety, but demonstrated no significant deficits in global cognitive functions or executive function compared to the control group. Increased age in carriers was significantly associated with increased anxiety levels. As expected, FMR1 mRNA expression was significantly correlated with CGG repeat number. However, no significant correlations were observed between molecular (including epigenetic) measures and clinical phenotypes in this sample. Our study, albeit limited by the sample size, establishes the complexity of the mechanisms that link the FMR1 locus to the clinical phenotypes commonly observed in female carriers suggesting that other factors, including environment or additional genetic changes, may have an impact on the clinical phenotypes. However, it continues to emphasize the need for assessment and treatment of psychiatric problems in female premutation carriers.
Databáze: OpenAIRE
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