Screening for fragile X syndrome: a literature review and modelling study

Abstract

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Screening for Expanded Alleles of the FMR1 Gene in Blood Spots from Newborn Males in a Spanish Population

“…The estimated frequency of full mutation alleles in this Spanish cohort of 5267 males, 1/2633, is in line with results from recent population screening studies (see 1,8 ); however, since this estimate was based on only two samples, the confidence interval is quite large. Assuming that the observed frequency is correct, a sample size of approaching 50,000 would be needed to reduce the upper limit of the confidence interval to within about 25% of the mean value.…”

“…Although fragile X syndrome (FXS) is the most common inherited form of intellectual disability, prior estimates of the frequencies of expanded CGG-repeat alleles have varied widely, ranging from ϳ1/2000 to 1/8000, depending on the nature of ascertainment. 1 Estimates of fragile X syndrome disease prevalence, or FMR1 full mutation (Ͼ200 CGG repeats) allele frequency, derived from screening of special education needs populations will likely miss individuals with mild learning disabilities, particularly in females with favorable X-activation ratios. 2 Indeed, a higher full mutation allele frequency (1 in ϳ2500 females) was reported by Pesso et al, 3 who screened a large number of Israeli women in the general population.…”

“…1 However, there remains some uncertainty regarding the premutation allele frequencies 1,[3][4][5][6][7] due in part to lingering issues of ascertainment bias, 8 but also to real frequency differences across ethnic and regional populations. For example, in the screens of males and females in Eastern Canada, allele frequencies were estimated to be ϳ1/800 males and ϳ1/260 females.…”

Carrier screening in preconception consultation in primary care

“…Carrier frequency may be different again in other population groups, with no carriers found in 370 women screened in a Japanese study (Otsuka et al 2010) and 1,002 women from Taiwan (Huang et al 2003), although these were much smaller sample sizes. The feasibility, cost-effectiveness and cost-benefit of populationbased carrier screening for FXS have been widely discussed, with arguments generally in favour (Wildhagen et al 1998;Toledano-Alhadef et al 2001;Song et al 2003;Palomaki 1994;Finucane 1996;Meadows and Sherman 1996;Musci 2005). However, guidelines from the American College of Medical Geneticists state that population carrier screening for FXS is not recommended except within well-defined clinical research protocols ) because of the difficulties around counselling and education regarding the meaning and interpretation of results (McConkie-Rosell et al 2005).…”

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

“…FXS occurs most often in males, with an approximate incidence of 1 in 4000 (1 in 8000 females) [55]. Cognitive symptoms include ID and language deficits, whereas behavioral symptoms include hyperactivity and social deficits.…”