Genotype-.phenotype correlations in patients with friedreich's ataxia

Friedreich's ataxia (FA) is a recessive neurodegenerative disorder associated with an intronic GAA trinuclcotide repeat expansion in the X25 gene on chromosome 9q. Normal subjects have 7 to 22 repeats, whereas FA patients carry expanded alleles with 120-1700 repeats. We investigated 133 Italian FA patients from 122 families, and evaluated the correlations between clinical features and expansion size. One hundred and twenty-five patients carried the expansion (170-1200 repeats) on both alleles. Eight subjects were heterozygous for the expansion and are candidates for X25 gene point mutations. Among homozygous patients, 10% had late onset of disease (up to 48 years) and 9% had retained deep tendon reflexes. Expansion size was inversely correlated with age of onset and confinement to wheel-chair; and positively correlated with the presence of cardiomyopathy. Our data suggest significant contribution of both alleles to phenotype. The availability of molecular diagnosis is revealing that the spectrum of phenotypic expression of the disease is broader than previously stated.