A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan

Genetic analysis and SOD1 mutation screening in Iranian amyotrophic lateral sclerosis patients

“…These are impressive figures. The role of C90RF72 in ALS in Asian populations appears to be less (Ogaki et al, 2012;Tsai et al, 2012). In addition to its prominent role in ALS, C90RF72 is important because mutations in the gene are also a cause of frontotemporal dementia which has long been considered to be related to ALS (Lillo and Hodges, 2009;Neumann et al, 2006).…”

Genetics of amyotrophic lateral sclerosis in the Han Chinese

“…However, the reported frequencies in Asian samples have been lower. Four studies have reported a low frequency of HRE in Japanese ALS cases (0 -3.4% in fALS, and 0.4% sALS) [73,78,129,130] and a higher frequency was reported in cases from Taiwan of Han Chinese ancestry (18.2% in fALS, and 2.0% in sALS) [75]. In the present study, the author reports that the frequency of the C9orf72 HRE in Chinese sALS patients is 0.3%.…”

“…To date, this is the largest cohort screened in non-Caucasian ALS cases. Previous reports about C9orf72 HRE in different populations support the hypothesis that the pathogenic HRE arose from a single founder haplotype both in Caucasian and Asian populations [11,73,75,78,80,81,129,130], although for cases in Taiwan it was postulated that the HRE was introduced in the 17 th century when Taiwan was under Dutch and Spanish colonial rule. The conjecture that Asian HREs arose on the same European founder seems inconsistent with the mutation occurring in a founder 1,500 years ago [78].…”

“…Two Japanese studies report that the frequencies of the repeat expansion range from 0-3.4% in fALS and 0-0.4% in sALS [73,74]. In contrast, a small study in Taiwanese of Han Chinese ancestry reported higher frequencies of the repeat expansion (18.2% in fALS patients and 2.0% in sALS patients) [75]. The GGGGCC repeat has also been found in neurologically healthy controls (~0.2 %) as well as in Italian geriatric cases without ALS or dementia (1.2%) [71,[76][77][78][79].…”

“…Most reports about C9orf72 repeat expansion frequencies in different populations support the hypothesis that the pathogenic repeat expansion in C9orf72 arose from a single founder haplotype [11,67,80] both in Caucasian and Asian populations [73,75], as tagged by the A allele of rs3849942,which occurs in most reported C9orf72 GGGGCC repeatcarrying ALS cases and the A allele of rs2814707, which has been used as a significant genetic association marker of chromosome 9p21 in the Flanders-Belgian cohort of patients with FTLD, FTLD-ALS, and ALS (odds ratio 2.6, 95% CI 1.5-4.7; p=0.001). It has been estimated that the repeat expansion occurred once ~1,500 years ago [78].…”