Identification of a novel missense mutation in angiogenin in a Chinese amyotrophic lateral sclerosis cohort.
ABSTRACT Abstract Angiogenin (ANG) gene mutations have been identified in both familial and sporadic amyotrophic lateral sclerosis (ALS) patients from multiple European and North American populations. However, no ANG mutation has yet been reported in Asian ALS populations. Here, we screened for ANG mutations in a Chinese ALS cohort. The entire coding region of the ANG gene was sequenced in 10 familial ALS pedigrees, 202 sporadic ALS patients, and 151 healthy controls. All patients were negative for SOD1, FUS, and TARDBP mutations. We identified a novel missense mutation, c.379G > A (p.V103I), in one sporadic ALS patient, but not in the controls. No mutations were found in the familial ALS patients. A novel missense variant, c.323A > G (p.H84R), was detected in one healthy individual. We identified the presence of the known single nucleotide polymorphism, rs11701 (T/G), in both ALS cases and controls. However, no significant association of the G allele with ALS susceptibility was demonstrated. In conclusion, ANG mutations accounted for 0.5% of our SOD1-, FUS-, TARDBP- mutation-negative ALS cohort. Our findings highlight that the genetic background of ALS differs between different populations, and suggest that ANG mutation may be involved in the aetiology of ALS in the Han Chinese population.
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ABSTRACT: Certain single nucleotide polymorphisms causing missense mutations in angiogenin result in its loss-of-function and onset of amyotrophic lateral sclerosis (ALS). Although several such associations are reported across diverse ethnic groups, no method is available for predicting if a new mutation is deleterious. We present here a fast molecular dynamics based method for determining the mechanisms of functional loss caused by mutations, and attributes to ascertain whether a mutation causes ALS.FEBS letters 05/2013; · 3.54 Impact Factor
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ABSTRACT: Our objective was to examine trends and epidemiology of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) associated deaths in the United States. ALS/MND associated death rates and trends in the United States for 1999-2009 were examined using the multiple cause-of-death mortality data. Age-specific and age-adjusted death rates were calculated. For 1999-2009, the average annual age-adjusted death rate was 2.17/100,000 persons. The age-specific rate increased with age until 75-79 years. Males experienced a higher death rate than females. There was no definitive trend in the annual ALS/MND associated death rate, although analyses suggested a possible decrease (p = 0.05); however, the rate increased for persons 20-49 years of age and declined for persons ≥ 65 years of age. The annual rate for males decreased whereas the rate for females showed no change. In conclusion, the suggested decreasing annual ALS/MND associated death rate for 1999-2009 contrasts with earlier reports indicating that the incidence and death rate of ALS were increasing. While the ALS/MND associated death rate slightly increased among adults 20-49 years of age, rates declined among two subpopulations at higher risk for ALS/MND - males and persons ≥ 65 years of age. Continued monitoring of ALS/MND mortality data and additional epidemiological studies will be important to further elucidate these epidemiological trends.Amyotrophic lateral sclerosis & frontotemporal degeneration. 04/2013;