The Population Based Prevalence and Phenotype of 9p21 Hexanucleotide Repeats in ALS/FTD (S05.004)

Objective: To look at the clinical phenotype of Irish ALS patients testing positive for hexanucelotide repeat on chromosome nine. Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that overlaps with frontotemporal dementia. A hexanucleotide repeat on chromosome 9p21 has been associated with ALS and FTD. The population based frequency of this repeat and the cognitive phenotype in familial and sporadic ALS, has not been established. Design/Methods: 600 population-based samples from the Irish ALS DNA bank were tested using a combination of reverse prime PCR and capillary electrophoresis. 200 of these patients had undergone full neurocognitive profiling and 25% of these had undergone extensive neuroimaging with 3-T MRI. Results: 9.9% of the Irish ALS population had an expanded hexanucleotide repeat of greater than 30. 60% had a strong family history of ALS or FTD, and all had evidence of cognitive or behaviour impairment. A distinctive imaging signal could be identified in those with the repeat. The negative predictive value for patients with normal cognition and no family history was 100%. Patients with ALS/FTD and a family history had a positive predictive value of 80%. Conclusions: The 9p21 hexanucleotide repeat account for 40% of familial ALS in Ireland. The repeat does not associate with cognitively normal sporadic ALS. Supported by: HRB research grant. Disclosure: Dr. Byrne has nothing to disclose. Dr. Byrne has nothing to disclose. Dr. Bede has nothing to disclose. Dr. Elamin has nothing to disclose. Dr. Byrne has nothing to disclose. Dr. Byrne has nothing to disclose. Dr. McLaughlin has nothing to disclose. Dr. Pender has nothing to disclose. Dr. Byrne has nothing to disclose. Dr. Al-Chalabi has nothing to disclose. Dr. Hardiman has received personal compensation for activities with Ono Pharmaceuticals, Sanofi Aventis Pharmaceuticals, Inc., and Biogen Idec, Merck Serono and Schering AG as a committee member and/or serving on advisory panels.2. Dr. Hardiman has received personal compensation in an editorial capacity for the Amyotrophic Lateral Sclerosis Journal.