C9orf 72 repeat expansions in a Canadian provincial cohort (P2.066)

OBJECTIVE: To determine the referral indication, family history and clinical test sensitivity of C9orf72. BACKGROUND: The Chromosome 9 open reading frame 72 (C9orf72) gene, located on chromosome 9p21 contains a hexanucleotide GGGGCC repeat located in a non-coding region. Normal range is 2 to 23 repeats, with repeats greater than 30 considered pathogenic. These are inherited in an autosomal dominant fashion. Repeats between 23 to 30 are of intermediate significance. Research has demonstrated this repeat expansion as the most common cause of familial Amyotrophic Lateral Sclerosis (ALS) and Fronto- Temporal Dementia (FTD) with a worldwide incidence of 34[percnt] and 25[percnt] respectively. Clinical testing for this expansion became available in Alberta in January 2013. All testing for C9orf72 mutations in Alberta is performed in one laboratory at the University of Alberta in Edmonton. DESIGN/METHODS: Using the Molecular Diagnostic laboratory database, we identified all requests for C9orf72 testing and reviewed patient data. RESULTS: To date, 59 patients (35 men, 24 women) have been tested, 35 for ALS, 13 FTD, 4 Atypical Parkinsonism and 4 Late onset ataxia (LOA). Family history was positive in 27 patients (14 ALS, 7 FTD, 3 Atypical Parkinsonism and 3 LOA). C9orf72 abnormalities were detected in 10 patients (7 ALS, 3 FTD); all had a positive family history. In the FTD phenotype, 1 pathogenic expansion, 1 homozygous expansion and 1 intermediate expansion were detected. In the ALS phenotype, 1 deletion and 6 pathogenic expansions were detected. No mutations were detected in the Atypical Parkinsonism, LOA phenotypes and sporadic cases. CONCLUSIONS: C9orf72 abnormalities were detected in 17[percnt] of total cases, with 23[percnt] positive in ALS and 20[percnt] positive in FTD, similar to rates seen in Western European populations. Lack of family history significantly decreases the possibility of a positive result. Study Supported by: Toupin Research Foundation, University of Alberta Disclosure: Dr. Venkitachalam has nothing to disclose. Dr. Hume has nothing to disclose. Dr. Ashtiani has nothing to disclose. Dr. Christian has nothing to disclose. Honoraium from UpToDate,