Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Identification and characterization of novel ERBB4 variant associated with sporadic amyotrophic lateral sclerosis (ALS)

Authors
Kwon, YounghwiKang, MinsungJeon, Yu-MiLee, ShinryeLee, Ho-WonPark, Jin-SungKim, Hyung-Jun
Issue Date
Feb-2024
Publisher
ELSEVIER
Keywords
Amyotrophic lateral sclerosis; ERBB4 N706D; Next generation sequencing
Citation
JOURNAL OF THE NEUROLOGICAL SCIENCES, v.457
Journal Title
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume
457
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/1156
DOI
10.1016/j.jns.2024.122885
ISSN
0022-510X
1878-5883
Abstract
Amyotrophic Lateral Sclerosis (ALS) is the most common type of motor neuron disease characterized by progressive motor neuron degeneration in brain and spinal cord. Most cases are sporadic in ALS and 5-10% of cases are familiar. >50 genes are known to be associated with ALS and one of them is ERBB4. In this paper, we report the case of a 53-year-old ALS patient with progressive muscle weakness and fasciculation, but he had no cognitive decline. We performed the next generation sequencing (NGS) and in silico analysis, it predicted a highly pathogenic variant, c.2116 A > G, p.Asn706Asp (N706D) in the ERBB4 gene. The amino acid residue is highly conserved among species. ERBB4 is a member of the ERBB family of receptor tyrosine kinases. ERBB4 has multiple tyrosine phosphorylation sites, including an autophosphorylation site at tyrosine 1284 residue. Autophosphorylation of ERBB4 promotes biological activity and it associated with NRG-1/ERBB4 pathway. It is already known that tyrosine 128 phosphorylation of ERBB4 is decreased in patients who have ALS-associated ERBB4 mutations. We generated ERBB4 N706D construct using site-directed mutagenesis and checked the phosphorylation level of ERBB4 N706D in NSC-34 cells. We found that the phosphorylation of ERBB4 N706D was decreased compared to ERBB4 wild-type, indicating a loss of function mutation in ERBB4. We report a novel variant in ERBB4 gene leading to ALS through dysfunction of ERBB4.
Files in This Item
There are no files associated with this item.
Appears in
Collections
연구본부 > 치매 연구그룹 > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Jeon, Yu-Mi photo

Jeon, Yu-Mi
연구본부 (치매 연구그룹)
Read more

Altmetrics

Total Views & Downloads

BROWSE