Prevalence of the fragile X syndrome in African‐Americans

Abstract

Since the development of a molecular diagnosis for the fragile X syndrome in the early 1990s, several population-based studies in Caucasians of mostly northern European descent have established that the prevalence is probably between one in 6,000 to one in 4,000 males in the general population. Reports of increased or decreased prevalence of the fragile X syndrome exist for a few other world populations; however, many of these are small and not population-based. We present here the final results of a 4-year study in the metropolitan area of Atlanta, Georgia, establishing the prevalence of the fragile X syndrome and the frequency of CGG repeat variants in a large Caucasian and African-American population. Results demonstrate that one-quarter to one-third of the children identified with the fragile X syndrome attending Atlanta public schools are not diagnosed before the age of 10 years. Also, a revised prevalence for the syndrome revealed a higher point estimate for African-American males (1/2,545; 95% CI: 1/5,208-1/1,289) than reported previously, although confidence intervals include the prevalence estimated for Caucasians from this (1/3,717; 95% CI: 1/7,692-1/1,869) and other studies. Further population-based studies in diverse populations are necessary to explore the possibility that the prevalence of the fragile X syndrome differs among world populations.

Fragile X–related element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study

“…35 Depending on test volume, the approximate cost for inclusion of FXS into newborn screening using FREE2 methylation analysis would be between $700,000 and $1.5 million for every 100,000 babies tested (i.e., lower cost with greater test volume). On the basis of the previously reported FM frequency range (between 1 in 2,000 and 1 in 3,600 in the general population) 14 and the fact that approximately half of all FM females will be identified using the FREE2 test, we estimate that between 21 and 38 FXS-affected individuals (and their families) will be identified for every 100,000 newborns screened.…”

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

“…300624) is the most common form of inherited intellectual disabilities (IDs), with an estimated incidence of 1 in 4000 males and 1 in 8000 females. 1,2 The molecular basis of this syndrome is mainly the expansion of an unstable region of CGG repeats in the 5¢-untranslated region of the FXS gene (FMR1). The CGG repeat of the FMR1 gene is distributed in the population in four allelic classes.…”

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