Intractable Rare Dis Res. 2014;3(4):153-161. (DOI: 10.5582/irdr.2014.01028)

Distribution of AGG interruption patterns within nine world populations.

Yrigollen CM, Sweha S, Durbin-Johnson B, Zhou L, Berry-Kravis E, Fernandez-Carvajal I, Faradz SMH, Amiri K, Shaheen H, Polli R, Murillo-Bonilla L, de Jesus Silva Arevalo G, Cogram P, Murgia A, Tassone F

The CGG trinucleotide repeat within the FMR1 gene is associated with multiple clinical disorders, including fragile X-associated tremor/ataxia syndrome, fragile X-associated primary ovarian insufficiency, and fragile X syndrome. Differences in the distribution and prevalence of CGG repeat length and of AGG interruption patterns have been reported among different populations and ethnicities. In this study we characterized the AGG interruption patterns within 3,065 normal CGG repeat alleles from nine world populations including Australia, Chile, United Arab Emirates, Guatemala, Indonesia, Italy, Mexico, Spain, and United States. Additionally, we compared these populations with those previously reported, and summarized the similarities and differences. We observed significant differences in AGG interruption patterns. Frequencies of longer alleles, longer uninterrupted CGG repeat segments and alleles with greater than 2 AGG interruptions varied between cohorts. The prevalence of fragile X syndrome and FMR1 associated disorders in various populations is thought to be affected by the total length of the CGG repeat and may also be influenced by the AGG distribution pattern. Thus, the results of this study may be important in considering the risk of fragile X-related conditions in various populations.

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