Publication
Title
Truncating SLC5A7 mutations underlie a spectrum of dominant hereditary motor neuropathies
Author
Abstract
Objective To identify the genetic cause of disease in 2 previously unreported families with forms of distal hereditary motor neuropathies (dHMNs). Methods The first family comprises individuals affected by dHMN type V, which lacks the cardinal clinical feature of vocal cord paralysis characteristic of dHMN-VII observed in the second family. Next-generation sequencing was performed on the proband of each family. Variants were annotated and filtered, initially focusing on genes associated with neuropathy. Candidate variants were further investigated and confirmed by dideoxy sequence analysis and cosegregation studies. Thorough patient phenotyping was completed, comprising clinical history, examination, and neurologic investigation. Results dHMNs are a heterogeneous group of peripheral motor neuron disorders characterized by length-dependent neuropathy and progressive distal limb muscle weakness and wasting. We previously reported a dominant-negative frameshift mutation located in the concluding exon of the SLC5A7 gene encoding the choline transporter (CHT), leading to protein truncation, as the likely cause of dominantly-inherited dHMN-VII in an extended UK family. In this study, our genetic studies identified distinct heterozygous frameshift mutations located in the last coding exon of SLC5A7, predicted to result in the truncation of the CHT C-terminus, as the likely cause of the condition in each family. Conclusions This study corroborates C-terminal CHT truncation as a cause of autosomal dominant dHMN, confirming upper limb predominating over lower limb involvement, and broadening the clinical spectrum arising from CHT malfunction.
Language
English
Source (journal)
Neurology : Genetics / American Academy of Neurology. - 2015, currens
Publication
2018
ISSN
2376-7839
Volume/pages
4:2(2018), 8 p.
Article Reference
UNSP e222
ISI
000430503200001
Pubmed ID
29582019
Medium
E-only publicatie
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Project info
Tackling the missing heritability of inherited peripheral neuropathies: towards improved patient care, better mechanistic insights and identification of determinants driving phenotypic diversity.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 04.05.2018
Last edited 21.08.2021
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