Founder effect in a Belgian-Dutch fragile X population

✍ Scribed by Sonja Buyle; Edwin Reyniers; Lieve Vits; Kristel Boulle; Ingrid Handig; Floris L. E. Wuyts; Wout Deelen; Dicky J. J. Halley; Ben A. Oostra; Patrick J. Willems

• Book ID: 104680154
• Publisher: Springer
• Year: 1993
• Tongue: English
• Weight: 381 KB
• Volume: 92
• Category: Article
• ISSN: 0340-6717
• DOI: 10.1007/bf00244471

✦ Synopsis

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.