FRAXE in the Newfoundland population

Dohey, Amanda (2018) FRAXE in the Newfoundland population. Masters thesis, Memorial University of Newfoundland.

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Abstract

Children, especially boys, can present to their primary care physician, pediatrician, or genetics program with developmental delay and/or intellectual disability. FRAXE is a rare cause of intellectual disability caused by expansion and methylation of the CCG repeats in the 5’ untranslated region of the FMR2 gene. Although the phenotype associated with FRAXE is not well defined, it has been reported to include: mild (IQ 50-69) to borderline (70-79) intellectual disability, learning problems, communication problems and overactivity with no consistent dysmorphology. In the Canadian province of Newfoundland and Labrador, prior to initiation of the current study, two families segregating FMR2 expansions had been identified. The purpose of this study was to determine the prevalence of FRAXE among boys referred to the Provincial Medical Genetic Program for intellectual disability and/or developmental delay; to characterize FRAXE positive families; and to determine if there is a common ancestor connecting these families. This was accomplished by reviewing the charts of boys seen in the Provincial Medical Genetics Program from 1994 to 2004 that had unexplained developmental delay. This review resulted in the discovery of a FRAXE positive boy and his full mutation sister. During this time two additional FRAXE families were referred to the Provincial Medical Genetics Program. Using microsatellite markers three of the four FRAXE positive families were found to share a common haplotype of 1.8 Mb. The minimum prevalence rate in this male pediatric population was found to be 1 in 7737 which is a six fold increase compared with the reported prevalence rate for FRAXE of 1 in 50,000 or 1 in 23,423. Our data supports routine testing of FMR2 expansions in boys with intellectual disability in the NL population.

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