Analysis of the C9orf72 hexanucleotide repeat expansion in Korean patients with familial and sporadic amyotrophic lateral sclerosis

Jang, Ja Hyun; Kwon, Min Jung; Choi, Won Jun; Oh, Ki‐Wook; Koh, Seong Ho; Ki, Chang Seok; Kim, Seung H.

doi:10.1016/j.neurobiolaging.2012.09.004

Cited by 64 publications

(41 citation statements)

References 10 publications

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“…Our meta-analysis showed that, in mainland China, FUS is the most commonly mutated gene in SALS (1.9%) and the second most commonly mutated gene (7.1%) in FALS, with a frequency similar to that of the Taiwanese population (FALS: 6.7%, SALS: 1.5%),8 slightly lower than results from Korea (FALS: 11.1%; SALS: 1.2%),9 but much higher than those of Caucasians 2–6. Population comparisons showed that FUS mutations were significantly more common among mainland Chinese patients than those among Caucasian populations (p=6.8×10 −3 ).…”

Section: Discussionmentioning

confidence: 56%

The distinctive genetic architecture of ALS in mainland China: Table 1

Zou

Liu

2015

J Neurol Neurosurg Psychiatry

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Section: Discussionmentioning

confidence: 56%

The distinctive genetic architecture of ALS in mainland China: Table 1

Zou

Liu

2015

J Neurol Neurosurg Psychiatry

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“…However, the preliminary evidence suggested that the C9orf72 mutation rates in patients with clinically diagnosed ALS in China, Japan, Korea, and Taiwan were much lower than that observed in Caucasian populations (Ogaki et al, 2012; Tsai et al, 2012; Zou et al, 2012; Jang et al, 2013), which implied that the number of repeats varied greatly due to different nationalities and ethnicities. Given the clinical heterogeneity with the repeat expansions, we hypothesized that the length of repeats may also account for other neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 95%

C9orf72 mutation is rare in Alzheimer's disease, Parkinson's disease, and essential tremor in China

Jiao

Guo

Wang

et al. 2013

Front. Cell. Neurosci.

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GGGGCC repeat expansions in the C9orf72 gene have been identified as a major contributing factor in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Given the overlapping of clinical phenotypes and pathological characteristics between these two diseases and Alzheimer's disease (AD), Parkinson's disease (PD), and essential tremor (ET), we speculated regarding whether C9orf72 repeat expansions also play a major role in these three diseases. Using the repeat-primed polymerase chain reaction method, we screened for C9orf72 in three groups of patients with PD (n = 911), AD (n = 279), and ET (n = 152) in the Chinese Han population. There were no pathogenic repeats (>30 repeats) detected in either the patients or controls (n = 314), which indicated that the pathogenic expansions of C9orf72 might be rare in these three diseases. However, the analysis of the association between the number of repeats (p = 0.001), short/intermediate genotype (short: <7 repeats; intermediate: ≥7 repeats) (odds ratio 1.37 [1.05, 1.79]), intermediate/intermediate genotype (Odds ratio 2.03 [1.17, 3.54]), and PD risks indicated that intermediate repeat alleles could act as contributors to PD. To the best of our knowledge, this study is the first to reveal the correlation between C9orf72 and Chinese PD, AD, or ET patients. Additionally, the results of this study suggest the novel idea that the intermediate repeat allele in C9orf72 is most likely a risk factor for PD.

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“…9 Both patients in the latter study with 22 repeats exhibited cognitive and behavioural impairment similar to larger expansions and had family history of FTD, while two patients with 20 and 21 repeats had family history of dementia and psychiatric illness. In atypical PD or PD with psychosis, intermediate expansions (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) were detected in three female cases with atypical parkinsonian syndromes (severe rigid akinetic parkinsonism) and neuropsychiatric symptoms including schizoaffective psychosis and an FTD-like dementia. 42 Unfortunately, these cases did not have pathological diagnosis.…”

Section: Original Articlementioning

confidence: 99%

“…16 Homozygous 56 57 ► TDP43 formation may be 'age-related' findings; pathological studies found no expansion or intermediate alleles (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) repeats) among LRRK2 G2019S carriers and AD cases with concomitant TDP43-positive inclusions. 16 Variation of large-normal and intermediate C9orf72 repeat lengths by ethnicity needs to be determined ► European haplotype exists in Asian cohorts, 25 27 49 but at a lower frequency (<2% in Chinese controls compared with 9% in European controls).…”

Section: Effect Of Homozygosity Versus Heterozygosity Of Normal and Imentioning

confidence: 99%

Intermediate C9orf72 alleles in neurological disorders: does size really matter?

Tan

2017

J Med Genet

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C9orf72 repeat expansions is a major cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Sizes of <20 hexanucleotide repeats are observed in controls, while up to thousands associate with disease. Intermediate C9orf72 repeat lengths, however, remain uncertain. We systematically reviewed the role of intermediate C9orf72 alleles in C9orf72-related neurological disorders. We identified 49 studies with adequate available data on normal or intermediate C9orf72 repeat length, involving subjects with FTD, ALS, Parkinson’s disease (PD), atypical parkinsonism, Alzheimer’s disease (AD) and other aetiologies. We found that, overall, normal or intermediate C9orf72 repeat lengths are not associated with higher disease risk across these disorders, but intermediate allele sizes appear to associate more frequently with neuropsychiatric phenotypes. Intermediate sizes were detected in subjects with personal or family history of FTD and/or psychiatric illness, parkinsonism complicated by psychosis and rarely in psychiatric cohorts. Length of the hexanucleotide repeat may be influenced by ethnicity (with Asian controls displaying shorter normal repeat lengths compared with Caucasians) and underlying haplotype, with more patients and controls carrying the ‘risk’ haplotype rs3849942 displaying intermediate alleles. There is some evidence that intermediate alleles display increased methylation levels and affect normal transcriptional activity of the C9orf72 promoter, but the ‘critical’ repeat size required for initiation of neurodegeneration remains unknown and requires further study. In common neurological diseases, intermediate C9orf72 repeats do not influence disease risk but may associate with higher frequency of neuropsychiatric symptoms. This has important clinical relevance as intermediate carriers pose a challenge for genetic counselling.

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Analysis of the C9orf72 hexanucleotide repeat expansion in Korean patients with familial and sporadic amyotrophic lateral sclerosis

Cited by 64 publications

References 10 publications

The distinctive genetic architecture of ALS in mainland China: Table 1

The distinctive genetic architecture of ALS in mainland China: Table 1

C9orf72 mutation is rare in Alzheimer's disease, Parkinson's disease, and essential tremor in China

Intermediate C9orf72 alleles in neurological disorders: does size really matter?

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