title: Founder effect in a Belgian-Dutch fragile X population.
abstract: For many years, the high prevalence of the fragile X syndrome was thought to be caused by a high mutation frequency. The recent isolation of the FMR1 gene and identification of the most prevalent mutation enable a more precise study of the fragile X mutation. As the vast majority of fragile X patients show amplification of an unstable trinucleotide repeat, DNA studies can now trace back the origin of the fragile X mutation. To date, de novo mutations leading to amplification of the CGG repeat have not yet been detected. Recently, linkage disequilibrium was found in the Australian and US populations between the fragile X mutation and adjacent polymorphic markers, suggesting a founder effect of the fragile X mutation. We present here a molecular study of Belgian and Dutch fragile X families. No de novo mutations could be found in 54 of these families. Moreover, we found significant (P < 0.0001) linkage disequilibrium in 68 unrelated fragile X patients between the fragile X mutation and an adjacent polymorphic microsatellite at DXS548. This suggests that a founder effect of the fragile X mutation also exists in the Belgian and Dutch populations. Both the absence of new mutations and the presence of linkage disequilibrium suggest that a few ancestral mutations are responsible for most of the patients with fragile X syndrome.
authors.affiliation: Department of Medical Genetics, University of Antwerp-UIA, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Buyle
authors.forename: E
authors.initials: E
authors.lastname: Reyniers
authors.forename: L
authors.initials: L
authors.lastname: Vits
authors.forename: K
authors.initials: K
authors.lastname: De Boulle
authors.forename: I
authors.initials: I
authors.lastname: Handig
authors.forename: F L
authors.initials: FL
authors.lastname: Wuyts
authors.forename: W
authors.initials: W
authors.lastname: Deelen
authors.forename: D J
authors.initials: DJ
authors.lastname: Halley
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: P J
authors.initials: PJ
authors.lastname: Willems
mesh_terms: D000483:Alleles; D001530:Belgium / Q000453:epidemiology; D016009:Chi-Square Distribution; D005260:Female; D005600:Fragile X Syndrome / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D017720:Molecular Epidemiology; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D012091:Repetitive Sequences, Nucleic Acid