FMR1 MRNA from Full Mutation Alleles is Associated with ABC-C Scores in Males with Fragile X Syndrome

Overview

Journal Sci Rep

Specialty Science

Date 2020 Jul 18

PMID 32678152

Citations 8

Authors

Emma K Baker

Marta Arpone

Claudine Kraan

Minh Bui

Carolyn Rogers

Michael Field

Lesley Bretherton

Ling Ling

Alexandra Ure

Jonathan Cohen

Matthew F Hunter

Lorena Santa Maria

Victor Faundes

Bianca Curotto

Paulina Morales

Cesar Trigo

Isabel Salas

Angelica Alliende

David J Amor

David E Godler

Affiliations

Soon will be listed here.

Abstract

Fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥ 200 CGG repeats, and a decrease in FMR1 mRNA and its protein. However, incomplete silencing from FM alleles has been associated with more severe autism features in FXS males. This study compared scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-C) in 62 males affected with FXS (3 to 32 years) stratified based on presence or absence of mosaicism and/or FMR1 mRNA silencing. Associations between ABC-C subscales and FMR1 mRNA levels, assessed using real-time PCR relative standard curve method, were also examined. The FXS group mosaic for premutation (PM: 55-199 CGGs) and FM alleles had lower irritability (p = 0.014) and inappropriate speech (p < 0.001) scores compared to males with only FM alleles and complete loss of FMR1 mRNA. The PM/FM mosaic group also showed lower inappropriate speech scores compared to the incomplete silencing (p = 0.002) group. Increased FMR1 mRNA levels were associated with greater irritability (p < 0.001), and lower health-related quality of life scores (p = 0.004), but only in the incomplete silencing FM-only group. The findings suggest that stratification based on CGG sizing and FMR1 mRNA levels may be warranted in future research and clinical trials utilising ABC-C subscales as outcome measures.

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