title: Apparent anticipation in SOD1 familial amyotrophic lateral sclerosis.
abstract: Although anticipation has been previously reported in the copper/zinc superoxide dismutase-1 (SOD1) associated familial amyotrophic lateral sclerosis (FALS), some have argued that this may represent ascertainment bias. Consequently, the aim of the present study was to determine whether anticipation was a feature in SOD1 FALS. From a cohort of 112 individuals, the clinical and genetic history of 34 SOD1 patients was assessed. Clinical history was collected with the age of death and disease duration determined in successive generations (generation 1, grandparent; generation 2, parents; generation 3, children), from five large SOD1 families. Results showed that the age of death was significantly less in generation 3 (40.1 ± 2.8 years) compared to generation 2 (46.2 ± 2.0 years, p < 0.05) and generation 1 (56.7 ± 4.5 years, p < 0.01). Furthermore, disease duration was longer in generation 1 (18.4 ± 3.7 months) compared to the disease duration in generation 2 (12.6 ± 2.6 months) and generation 3 (12.3 ± 1.9 months, p = 0.08). Positive intergenerational differences were evident in 92% of parent-offspring transmissions in the present SOD1 FALS cohort (c(2) = 70.6, p < 0.001). In conclusion, the present study supports anticipation as a phenomenon in FALS, possibly due to co-inheritance of modifier genes.
authors: Sydney Medical School, Westmead, University of Sydney, Wentworthville, NSW 2145, Sydney, Australia. s.vucic@neura.edu.au
authors: Steve
authors: S
authors: Vucic
authors: Garth A
authors: GA
authors: Nicholson
authors: Adriano
authors: A
authors: Chio
authors: Matthew C
authors: MC
authors: Kiernan
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D020132:Anticipation, Genetic; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1