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Han family with essential tremor caused by the P421L variant of the TENM4 gene in China.
Chi, Wu; Wu, Min; Wang, Han-Lu; Wu, Qiu-Yan; Zhang, Yan-Ping; Hu, Ya-Nan; Zhu, Yao-Bin; Lin, Xin-Fu; Chen, Ting; Luo, Jie-Wei; Ruan, Xing-Lin; Li, Yun-Fei.
Affiliation
  • Chi W; Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • Wu M; Emergency Department, Fujian Provincial Hospital, Fuzhou, 350001, China.
  • Wang HL; Fujian Provincial Key Laboratory of Emergency Medicine, Fujian Provincial Institute of Emergency MedicineFujian Emergency Medical Center, Fuzhou, 350001, China.
  • Wu QY; Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • Zhang YP; Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • Hu YN; Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • Zhu YB; Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • Lin XF; Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • Chen T; Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • Luo JW; Department of Traditional Chinese Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
  • Ruan XL; Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • Li YF; Department of Pediatrics, Fujian Provincial Hospital, Fuzhou, 350001, China.
Neurol Sci ; 44(6): 2003-2015, 2023 Jun.
Article in En | MEDLINE | ID: mdl-36689009
ABSTRACT

BACKGROUND:

Essential tremor (ET) is an autosomal dominant inheritance disorder. Mutations in fusion sarcoma (FUS), mitochondrial serine peptidase 2 (HTRA2), teneurin transmembrane protein 4 (TENM4), sortilin1 (SORT1), SCN11A, and notch2N-terminal-like (NOTCH2NLC) genes are associated with familial ET.

METHODS:

A proband with ET was tested using whole-exome sequencing and repeat-primed polymerase chain reaction. Subsequently, the family members were screened for the suspected mutation, and the results were verified using Sanger sequencing. The relationship between pedigree and phenotype was also analyzed, and structural and functional changes in the variants were predicted using bioinformatics analysis.

RESULTS:

In a family with ET, the proband (III4) and the proband's father (II1), grandfather (I1), uncle (II2), and cousin (III5) all presented with involuntary tremors of both upper limbs. The responsible mutation was identified as TENM4 c.1262C > T (p.P421L), which showed genetic co-segregation in the family survey. AlphaFold predicted a change in the spatial position of TENM4 after the P421L mutation, which may have affected its stability. AlphaFold also predicted P421L to be a deleterious variation, which would lead to lower degrees of freedom of the TENM4 protein, thereby affecting the protein's structure and stability. According to the bioinformatics analysis, TENM4 (p.P421L) may reduce the signal reaching the nucleus by affecting the expression of TENM4 messenger RNA (mRNA), thereby impairing the normal oligodendrocyte differentiation process and leading to impaired myelination.

CONCLUSION:

This study revealed that the TENM4 (p.P421L) pathogenic missense variation was responsible for ET in the proband.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Essential Tremor Limits: Humans Country/Region as subject: Asia Language: En Journal: Neurol Sci Journal subject: NEUROLOGIA Year: 2023 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Essential Tremor Limits: Humans Country/Region as subject: Asia Language: En Journal: Neurol Sci Journal subject: NEUROLOGIA Year: 2023 Document type: Article Affiliation country: