Fragile X syndrome is due to an expanded CGG repeat in the 50 UTR of the FMR1 gene. According to repeat size, we distinguish four allele categories: normal (40 CGG), intermediate (46–60 CGG), premutated (55–200 CGG) and full mutated (4200 CGG). However, the boundaries among these categories are unclear, making it difficult to classify unstable alleles and to estimate the risk of expansion. We report a family with a proband, carrying a methylated full mutation with an amplification of 1.2 kb. PCR analysis demonstrated two alleles of 29 and 61 CGGs in the mother. Sequencing of the 61 CGG allele showed no AGG interruptions. Both mother’s sisters had two alleles of 31 and 44 CGGs, and the daughter of one of these had two alleles of 22 and 44 repeats, demonstrating stable transmission of the 44 CGG allele. The maternal grandfather was deceased, but haplotype reconstruction using markers DXS548 and FRAXAC1 demonstrated that he was carrier of the premutated allele. Furthermore, molecular analysis confirmed the same paternity with a probability of 99.79% for all the threensisters.

Expansion to full mutation of a FMR1 intermediate allele over two generations.

DOBOSZ, Marina;
2004

Abstract

Fragile X syndrome is due to an expanded CGG repeat in the 50 UTR of the FMR1 gene. According to repeat size, we distinguish four allele categories: normal (40 CGG), intermediate (46–60 CGG), premutated (55–200 CGG) and full mutated (4200 CGG). However, the boundaries among these categories are unclear, making it difficult to classify unstable alleles and to estimate the risk of expansion. We report a family with a proband, carrying a methylated full mutation with an amplification of 1.2 kb. PCR analysis demonstrated two alleles of 29 and 61 CGGs in the mother. Sequencing of the 61 CGG allele showed no AGG interruptions. Both mother’s sisters had two alleles of 31 and 44 CGGs, and the daughter of one of these had two alleles of 22 and 44 repeats, demonstrating stable transmission of the 44 CGG allele. The maternal grandfather was deceased, but haplotype reconstruction using markers DXS548 and FRAXAC1 demonstrated that he was carrier of the premutated allele. Furthermore, molecular analysis confirmed the same paternity with a probability of 99.79% for all the threensisters.
2004
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/151434
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