Identification of a novel missense mutation in angiogenin in a Chinese amyotrophic lateral sclerosis cohort

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.

Key words::

• Angiogenin
• missense mutation
• amyotrophic lateral sclerosis (ALS)
• genetics

Acknowledgments

We thank the patients and their families, as well as the healthy controls, for their cooperation in this study. We also thank all the anonymous reviewers for their helpful suggestions on quality improvement of our paper. This study was funded by the National Natural Science Foundation of China, and the International Cooperation and Exchange project of the National Natural Science Foundation of China. The funding organization had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.