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: The purpose of the study is to investigate the epidemiology and associated medical expenses of motor neuron diseases (MND) in Taiwan. Data from the National Health Insurance Research Database, involving diagnoses of MND and Certificates of Serious Accidents and Diseases, were retrieved from January 2000 to December 2005. Age- and sex-specific incidences of MND were estimated by dividing the incidence number by population data obtained from the Department of Statistics, Ministry of the Interior. In total, 1,554 patients with MND were identified. The average yearly incidence was 1.05 per 100,000 people. The male to female ratio was 1.51. The incidence rate, which was 1.25 in men and 0.84 in women, tended to increase with age, and peaked in the ranges of 65-69 years in men and 70-74 years in women. The expenses of the medical services associated with MND increased year by year, except for a sudden drop in inpatient expenses in 2005. The incidence of MND in Taiwan was 1.05 per 100,000/year, which was lower than that of Caucasians. The incidence had moderate male predominance and increased with age. With an aging population, case numbers and medical expenses associated with these diseases are expected to rise in future decades.Neuroepidemiology 10/2008; 31(3):159-66. · 2.37 Impact Factor
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ABSTRACT: Angiogenin (ANG) gene, coding for an angiogenic factor up-regulated by hypoxia and expressed in ventral horn motor neurons, is a novel candidate for the pathogenesis of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease characterized by the selective loss of cortical and spinal motor neurons. Missense mutations in ANG gene have been identified in two ALS populations from Northern Europe and North America, both in familial (FALS) and sporadic (SALS) patients, but they do not seem to be frequent in the Italian population. We performed a mutational screening in a large cohort of 737 Italian ALS patients, including 605 SALS and 132 FALS cases. We identified seven different mutations, five of which are novel, in nine patients (six SALS and three FALS), but not in 515 healthy controls. Three mutations are located in the signal peptide region, three in the coding sequence, and one in the 3' untranslated region. In our ALS population, the observed mutational frequency of ANG gene accounts for about 1.2%, with an overrepresentation of FALS (2.3%) compared to SALS (1%) cases. We also found the previously described I46V substitution in six patients and four controls, suggesting that this mutation may represent a benign variant, at least in the Italian population. Our results provide further evidence of a tight link between angiogenesis and ALS pathogenesis and suggest that mutations in ANG gene are associated with an increased risk to develop ALS.Neurogenetics 03/2008; 9(1):33-40. · 3.58 Impact Factor
- Neurology 02/2009; 72(3):287-8. · 8.25 Impact Factor