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Diagnosis and Prevention of Fragile-X Syndrome. From the Family Study to the Population Screening Programme: Eighteen Years of Activity

  • M.L. Giovannucci Uzielli (a1), S. Guarducci (a1), A. Cecconi (a1), S. Lenzi (a1), U. Ricci (a1), C. Balestrieri (a1), P. Petrocelli (a1) and E. Lapi (a1)...

Extract

Fragile-X syndrome, which derives its name from the expression of a fragile site (FRAXA) at Xq27.3 associated with the phenotype, has achieved distinction as the most common inherited cause of mental retardation. It is the first disorder shown to be due to dynamic mutation in heritable instable DNA.

In 1991 the mutation responsible for Fragile-X syndrome was delineated as an expansion of the trinucleotide (CGG) sequence within an evolutionarily conserved gene, at the position of the fragile-X site.

The DNA of the promoter in the 5' UTR region of FMR-1 gene becomes abnormally methylated when the CGG sequence exceeds approximately 230 repeats, resulting in the transcriptional suppression of FMR-1. Based on the length of CGG repeat in the FMR-1 gene, the alleles are usually classified as normal, premutation or full mutation. CGG instability correlates with the length of repeats and number of AGGs within the FMR-1 CGG tract. In a minority of cases the Fragile-X syndrome may be due to deletion, or to point mutation in the FMR-1 gene.

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Corresponding author

Human Genetics Center, Department of Paediatrics, University of Florence, Via Masaccio, 209, 50132 Firenze, Italy

References

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Diagnosis and Prevention of Fragile-X Syndrome. From the Family Study to the Population Screening Programme: Eighteen Years of Activity

  • M.L. Giovannucci Uzielli (a1), S. Guarducci (a1), A. Cecconi (a1), S. Lenzi (a1), U. Ricci (a1), C. Balestrieri (a1), P. Petrocelli (a1) and E. Lapi (a1)...

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