Abstract
Background. Hexanucleotide repeat expansion in the C9orf72 gene is the most significant cause of a large number of neurodegenerative diseases: frontotemporal degeneration (FTD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), etc. Several studies have shown the relationship with the neurodegenerative process for full (>40 GGGGCC copies) and intermediate (13–20) repeats expansion. Methylation of the C9orf72 gene can play an important role in the pathogenesis of FTD and ALS, but the mechanism has not been sufficiently studied.The objective is to investigate the status of methylation of the 5’-promotor region of the C9orf72 gene in patients with neurodegenerative disorders having full or intermediate expansion of GGGGCC-repeats.Materials and methods. We investigated the methylation status of the 5’-promoter region of full C9orf72 expansions in FTD/ALS patients (n = 12), of intermediate expansions in Parkinson’s disease patients (n = 8) and of non-expanded alleles in healthy controls (n = 8). Methylation status was determined via sequencing of amplified fragments of bisulfite-converted DNA.Results. We identified two cases (sibling) with the hypermethylation of the 5’-promoter region in the full C9orf72 expansions group. Patient A. (65 years old, male) had an atypical ALS presentation: an onset with head tremor, a long duration of ALS symptoms (9 years at this time), and cognitive impairments with a temporal lobes atrophy. The patient’s sister had a similar clinical phenotype. There were no cases of the promoter hypermethylation in the intermediate and control groups.Conclusion. This is the first data on the 5’-promoter region C9orf72 gene methylation in Russian population. The frequency of the promoter methylation in this group was 9.1 % that consistent with previous studies in other populations. Atypical clinical presentation may indicate a modifying effect of methylation in this area on the ALS phenotype.
Highlights
Hexanucleotide repeat expansion in the C9orf72 gene is the most significant cause of a large number of neurodegenerative diseases: frontotemporal degeneration (FTD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), etc
Methylation of the C9orf72 gene can play an important role in the pathogenesis of FTD and ALS, but the mechanism has not been sufficiently studied
We investigated the methylation status of the 5’-promoter region of full C9orf72 expansions in FTD/ALS patients (n = 12), of intermediate expansions in Parkinson’s disease patients (n = 8) and of non-expanded alleles in healthy controls (n = 8)
Summary
Оценка метилирования 5’-промоторной области гена C9orf у российских пациентов с нейродегенеративными заболеваниями. Цель исследования – изучить статус метилирования 5’-промоторной области гена C9orf у пациентов с нейродегенеративными заболеваниями, имеющих полную или промежуточную экспансию GGGGCC-повторов. Мы исследовали метилирование 5’-промоторной области гена C9orf в группе пациентов с полной экспансией и фенотипом БАС и / или ЛВД (n = 12), с промежуточной экспансией и фенотипом болезни Паркинсона (n = 8) и в конт рольной группе (n = 8). Выявлены 2 случая метилирования 5’-промоторной области гена C9orf у сибсов в группе пациентов с полной экспансией. Ни одного случая метилирования 5’-промоторной области гена C9orf в группе с промежуточной экспансией и контрольной группе не обнаружено. Нетипичная клиническая картина у выявленных пациентов может свидетельствовать о модифицирующем влиянии метилирования данной области на фенотип БАС. Illarioshkin Research Center of Neurology; 80 Volokolamskoe Shosse, Моscow 125367, Russia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
