About prevalence of Fragile X in the general population

Since the gene causing Fragile X was identified in 1991 the prevalence of the syndrome has considerably changed for a constant decrease.

In the 90ies prevalence was estimated 1 in 1200 males and 2400 females. But a serious study published in 2001 has brought new lights: Fragile X is affecting 1 in 4000 males and 1 in 8000 females (Crawford et al 2001 FMR1 and the fragile X syndrome: human genome epidemiology review published in Genetics in medicine – the most frequently quoted paper on prevalence).

Studies of females with full mutation refer a range that goes from 1:4000 to 1:6000 (1.Coffee B, Keith K, Albizua I, Malone T, Mowrey J, Sherman SL, et al. Incidence of Fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet. 2009;85:503–514. 2. Hirst MC, Knight SJ, Christodoulou Z, Grewal PK, Fryns JP, Davies KE. Origins of the fragile X syndrome mutation. J Med Genet. 1993;30(8):647–650.).
Women with symptoms, score  30% chance to have a normal intelligence quotient, 25% to have intellectual disability with IQ less than 70, learning deficit (60%) and emotional difficulties (70%), as showed in Hagerman RJ, Hagerman PJ. Fragile X Syndrome. 3. Baltimore: The John Hopkins University Press; 2002.

In http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756550/ published in October 2009, there have been 36124 newborn males being tested, 7 of them with the full mutation, giving 1:5161.

In Tassone et al. published in Genome Medicine in December 2012, http://genomemedicine.com/content/4/12/100, approx. 14000 male and female newborns (each approx. 7000) have been tested for the premutation, with the result of a prevalence of the premutation of 1:209 for females and 1:430 for males.

According to another recent study the premutation occurs in 1 in 259 females and 1 in 468 to 1 in 813 males (Seltzer et al 2012 Prevalence of CGG expansions of the FMR1 gene in a US population-based sample published in American Journal of Medical Genetics).

In a more recent paper, using meta-analysis of publications in the past (Epidemiology of Fragile X Syndrome: A systematic Review and Meta-analysis Hunter et al 2014 published in American Journal of Medical Genetics) frequencies of individuals with the full mutation in the total population have been estimated to approximately 1:7000 for males and 1:11000 for females, with the frequencies of individuals with the premutation in the total population being estimated to approximately 1:850 for males and 1:300 for females.

However, trusting the most recent direct, extensive studies mentioned above we believe that the prevalence of people with the full mutation is closer to 1:5000 for both genders, with a premutation probability of 1:250 in females and 1:500 in males.