Prevalence of CGG expansions of the FMR1 gene in a US population‐based sample

Abstract

The primary goal of this study was to calculate the prevalence of the premutation of the FMR1 gene and of the “gray zone” using a population-based sample of older adults in Wisconsin (n=6,747 samples screened). Compared with past research, prevalence was relatively high (1 in 151 females and 1 in 468 males for the premutation and 1 in 35 females and 1 in 42 males for the gray zone as defined by 45–54 CGG repeats). A secondary study goal was to describe characteristics of individuals found to have the premutation (n = 30, 7 males and 23 females). We found that premutation carriers had a significantly higher rate of divorce than controls, as well as higher rates of symptoms that might be indicative of fragile X-associated tremor ataxia syndrome (FXTAS; numbness, dizziness/faintness) and fragile X primary ovarian insufficiency (FXPOI; age at last menstrual period). Although not statistically significant, premutation carriers were twice as likely to have a child with disability.

Genetic defects behind fragile X‐related disorders more common

“…Findings for the prevalence of premutation in girls by Tassone et al are consistent with previous studies, but these researchers observed in males a prevalence almost double that shown in a Canadian study [Dombroski et al, 2002], and are in line with a recent populationbased screening study of older adults in Wisconsin [Seltzer et al, 2012].…”

Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back

“…The CGG sequence is transcribed into the 5' untranslated region of FMR1 mRNA and thus length of the repeat sequence does not affect the sequence of the protein product of FMR1 [fragile X mental retardation protein (FMRP)] [2]. Small expansions in the gene , termed the Bpremutation^, occur in about 1 in 430-468 males and 1 in 151-209 females in the USA [3,4], and is associated with risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Although the premutation is transcribed and translated to give FMRP, toxicity in fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency is thought to occur through a mechanism related to elevated cellular FMR1 mRNA levels and resultant CGG repeatmediated RNA toxicity [2].…”

Distribution of AGG interruption patterns within nine world populations

“…DNA isolation and AGG interruption genotyping were performed at the UC Davis MIND Institute Molecular Laboratory as previously described (25,32), except 67 alleles extracted and genotyped in Italy, following IRB approved protocols at the correspondent institutions. Only AGG interruption patterns of unrelated normal alleles less than or equal to 40 CGG repeats in length, therefore within the normal size range (33)(34)(35), were included in the study.…”