The distinct genetic pattern of ALS in Turkey and novel mutations

Abstract

The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population.

Elevated Global DNA Methylation Is Not Exclusive to Amyotrophic Lateral Sclerosis and Is Also Observed in Spinocerebellar Ataxia Types 1 and 2

“…The extracted gDNAs were then stored at –20°C. ALS samples were classified as sALS with no family history of the disease [12, 13, 45-49] and familial ALS (fALS) in cases of family history of the disease or mutations in ALS-associated genes, including C9orf72 , SOD1 , FUS , TARDBP , and UBQLN2 , as previously mentioned and described in detail [50]. The majority of ALS samples was also additionally subjected to whole-exome and whole-genome analysis and only sALS patients with no known ALS-associated mutations were selected for this study.…”

Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD)

“…This is not the case for SOD1, FUS, or TARDBP mutations, which have been reported at similar percentages in a wide array of patient populations. On the other hand, the C9orf72 repeat expansion, which is a less penetrant mutation, is the most common mutation in studies of pan-European and North American patient populations [43,44], as well as in a recent study in a Turkish cohort [102], but is not as common among Chinese, Korean, and Japanese ALS patients [103][104][105].…”

Two Families with SOD1 (L144F) and C9orf72 Gene Mutations and an Overview of Amyotrophic Lateral Sclerosis

“…Approximately 5-10% of patients with ALS are thought to have FALS and the remainder has SALS. FALS often shows as autosomal dominant but rarely there is an X-linked or autosomal recessive inheritance pattern (11,12). The most common gene mutations related with FALS are C9orf72, SOD1, TDP43, FUS and ubiquilin 2 (UBQLN2).…”

“…The most common gene mutations related with FALS are C9orf72, SOD1, TDP43, FUS and ubiquilin 2 (UBQLN2). Mutations in the ALS2, senataxin, dynactin, angiogenin, optineurin, and spatacsin genes are relatively rare mutations related with FALS (12,13,14).…”