Analysis of C9orf72 repeat expansions in Georgian patients with ALS

Abstract BACKGROUNDAmyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the C9orf72 gene being the most significant. However, the presence of c9orf72 repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyze its frequency in Georgian patients with ALS.MethodsWe included 47 self-reported Georgian patients with ALS from different parts of the country, fulfilling the Gold Coast criteria. To investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene, we performed Repeat-Primed PCR. Results45 sporadic and 2 familial ALS cases were identified. Patients were aged 26 to 84 years with a mean age of 58.3 years at disease onset. Bulbar onset was observed in 21.3%, upper limb onset in 38.3%, and lower limb onset in 40.4% of the patients. Frontotemporal dementia (FTD) fulfilling the Strong criteria was diagnosed in 6 patients (12.7%). C9orf72 repeat expansion could not be detected in any of the cases using RP-PCR. ConclusionsOur results indicate that c9orf72 hexanucleotide expansion does not belong to the genetic risk factors of ALS in Georgian patients. Further genetic studies in a bigger study population are needed to reveal the genetic causes of ALS in the Transcaucasian population. As part of this research, Whole Exome Sequencing testing will be performed for identifying other gene mutations that might contribute to developing ALS in those patients.