Incidence of Fragile X in 5,000 Consecutive Newborn Males

Abstract

Fragile X syndrome (FXS) is the commonest cause of inherited mental retardation in males. Even though this affirmation is repeated in virtually all papers referring to FXS, the precise frequency of this syndrome in the general population is unknown. We present a general population screening analyzing an anonymous series of 5,000 consecutive newborn males from the neonatal screening program of the population of Catalonia in Spain. The aim of the study is to determine the incidence of FXS via a simple and economical methodology based on the nonamplification of the fragment containing the CGG repeats of the FRAXA locus in the samples carrying alleles over 52 repeats. From the initial 5,000 samples, 4,920 were in the normal range, 15 gave rise to bands with more than 52 repeats (11 corresponded to intermediate alleles and four premutated alleles). After further studies, two samples were considered to be carriers of full mutations. According to these results, the incidence of FXS affected newborn males is 1 in 2,466, and 1 in 1,233 males is a carrier of the premutation. We can deduce that 1 in 8,333 is an affected female with clinical manifestations and 1 in 411 will be a premutation carrier woman. Upon reviewing the literature, there seems to be variability in the frequencies found by the different groups. Therefore, given that our study is limited to the Catalan population in Spain, these results should be taken as valid for the Catalan region and should only be extrapolated to other populations with caution.

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

“…In a previous screen for expanded FMR1 alleles using blood spots, Rife et al 31 presented a general population screening of 4937 newborn blood spots from males collected throughout the Catalonia region in Spain. The screening yielded a frequency of 1/2466 full mutation males and 1/1233 premutation carriers.…”

Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families

“…In a study conducted in Catalonia we found an incidence of 1:2466 male and 1:8333 females. 1 This difference between males and females is because of the reduced penetrance of FXS in females. It is also important to highlight the high incidence of premutation carriers (55 -200 CGG repeats) in the general population, which has been estimated in 1 of 813 males and 1 of 259 females.…”

Neuroimaging - Clinical Applications

“…The real incidence of the syndrome is not known, but epidemiological studies indicate that it is responsible for mental retardation in 1 in 4,000-6,000 males and in 1 in 7,000-10,000 females of European descendent (for review Hagerman, 2002). In a study performed in Catalonia it gave an incidence of 1:2,466 male and 1:8,333 females (Rife et al, 2003). It is also important to highlight the high incidence of premutation carriers, 1 in 1,233 males and 1 in 411 females (Rife et al, 2003).…”