Novel mutation in optineurin causing aggressive ALS+/−frontotemporal dementia

Autor: Shu‐Man Feng, Chun‐Hui Che, Shu‐Yan Feng, Chang‐Yun Liu, Liu‐Yi Li, Yuan‐Xiao Li, Hua‐Pin Huang, Zhang‐Yu Zou
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Annals of Clinical and Translational Neurology, Vol 6, Iss 12, Pp 2377-2383 (2019)
Druh dokumentu: article
ISSN: 2328-9503
DOI: 10.1002/acn3.50928
Popis: Abstract Objective Mutations in optineurin (OPTN) have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS). We screened a cohort of Chinese patients for mutations in optineurin. We also performed an extensive literatures review of all mutations in optineurin identified previously to detect genotype–phenotype associations. Methods All 16 exons of the OPTN gene in a cohort of 15 familial ALS indexes and 275 sporadic ALS patients of Chinese origin were sequenced by targeted next generation sequencing. Results Two known heterozygous missense mutations in the OPTN, c.1481T> G (p.L494W), and c.1546G> C (p.E516Q), as well as one novel heterozygous missense mutation c.1690G> C (p.D564H) were each detected in one sporadic ALS patient. The patient carrying the p.E516Q mutation developed clinical features of ALS‐frontotemporal dementia (FTD) and the patient carrying the p.D564H mutation showed a phenotype of ALS. They both had an aggressive course, with a survival of 18 and 14 months respectively. Literature review showed that the clinical phenotypes in OPTN mutated ALS were not homogeneous, although some individuals showed a relatively slow progression and a long duration, some mutations carriers developed an aggressive progression and a short survival. Interpretation OPTN mutations contribute to ALS in Chinese population and account for 0.8% of sporadic ALS patients and 1.5% of familial ALS in the pooled Chinese ALS cohorts. Mutations in optineurin can cause aggressive ALS+/−FTD.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje