Molecular screening was performed in a cohort of 235 unrelated patients with adult-onset, autosomal dominant (17) or sporadic (218) cerebellar ataxia, negative for pathological trinucleotide expansions in the common SCAs, FRDA and FXTAS loci, by using targeted multigene panels or whole-exome sequencing.
These include symmetric T2 hyperintensity of the posterior and lateral columns of the cervical spinal cord in Friedreich ataxia, diffuse and symmetric hyperintensity of the cerebellar cortex in Infantile Neuro-Axonal Dystrophy, symmetric hyperintensity of the peridentate white matter in Cerebrotendineous Xanthomatosis, and symmetric hyperintensity of the middle cerebellar peduncles and peridentate white matter, cerebral white matter and corpus callosum in Fragile X Tremor Ataxia Syndrome.
Biochemical findings observed in FXTAS cells (lower mature frataxin, lower Complex IV and aconitase activities) along with common phenotypic traits shared by Friedreich's ataxia and FXTAS carriers (e.g. gait ataxia, loss of coordination) are consistent with a defective iron homeostasis in both diseases.
We have systematically investigated a population-based cohort of patients with chronic progressive LOCA for SCA 1, 2, 3, 6, 7, 8, 10, 12, 17, FXTAS and FRDA.