[Association between rare UBQLN2 variants and amyotrophic lateral sclerosis in Chinese population].
Zhonghua Yi Xue Za Zhi
; 101(12): 846-850, 2021 Mar 30.
Article
em Zh
| MEDLINE
| ID: mdl-33789365
ABSTRACT
Objective:
To explore the association between rare UBQLN2 variants and amyotrophic lateral sclerosis (ALS) in Chinese population, and the characteristic of phenotypes of their carriers.Methods:
A total of 166 ALS patients who visited Department of Neurology of Peking University Third Hospital between January 2018 and July 2020 were recruited. The next-generation sequencing was performed to screen possible pathogenic rare variants of UBQLN2. Meanwhile, control individuals were obtained from 1000 Genome Project (2 504 samples) and an in-house whole-exome sequencing database (1 812 samples), separately. The sequence kernel association test (SKAT) and the SKAT-optimal test (SKAT-O) were used to identify the association between UBQLN2 rare variants and ALS. The clinical characteristics of rare variant carriers were analyzed.Results:
A total of 33 familiar ALS and 133 sporadic ALS of Chinese ancestry were enrolled. Of the 166 ALS patients, 12.7% had bulbar-onset, 85.5% had limb-onset, and 5 cases were ALS with frontotemporal dementia (3.0%). The male-to-female ratio was 1.68â¶1, with a mean age at symptom onset of (43.8±12.2) years. Three possible pathogenic rare variants of UBQLN2 were detected, including c.128A>G (p.Lys43Arg), c.142G>T (p.Val48Leu) and c.1451T>G (p.Val484Gly), and all of them were novel missense mutations. Compared with 1000 Genome Project, SKAT and SKAT-O showed a P value of 2.49×10-6 and 9.22×10-7, respectively. While compared with the in-house database, SKAT and SKAT-O revealed a P value of 1.42×10-3 and 1.10×10-3, respectively. Patients who carried rare UBQLN2 variants were with a higher rate of bulbar-onset (2/3 vs 19/163, P=0.042).Conclusion:
Rare variants of UBQLN2 are associated with ALS in Chinese population, and mutation of UBQLN2 may be relevant to bulbar-onset.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esclerose Lateral Amiotrófica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
Zh
Ano de publicação:
2021
Tipo de documento:
Article