Evidence for high-risk haplotypes and (CGG)n expansion in fragile X syndrome in the Hellenic population of Greece and Cyprus

✍ Scribed by Syrrou, Maria; Patsalis, Philippos C.; Georgiou, Ioannis; Hadjimarcou, Michael I.; Constantinou-Deltas, C. D.; Pagoulatos, Gerassimos

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 32 KB
• Volume: 64
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(19960712)64:1<234::aid-ajmg42>3.0.co;2-l

✦ Synopsis

The expansion of the trinucleotide repeat (CGG)n in successive generations through maternal meiosis is the cause of fragile X syndrome. Analysis of CA repeat polymorphisms flanking the FMR-1 gene provides evidence of a limited number of "founder" chromosomes and predisposing high-risk haplotypes related to the mutation. To investigate the origin of mutations in the fragile X syndrome in the Hellenic populations of Greece and Cyprus, we studied the alleles and haplotypes at DXS548 and FRAXACS loci of 16 independent fragile X and 70 normal control chromosomes. In addition, we studied 191 unrelated normal X chromosomes for the distribution and frequencies of CGG alleles. At DXS548,6 alleles were found, 2 (194 and 196) of which were represented on fragile X chromosomes. At FRAXACS, 6 alleles were found, 4 of which were present on fragile X chromosomes. Sixteen haplotypes were identified, but only 5 were present on fragile X chromosomes. The highest number of CGG repeats (2 33) were associated with haplotypes 194-147, 194-151, 194-153, and 204-155. The data provide evidence for founder chromosomes and high-risk haplotypes in the Hellenic population.