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Clinical and Neuroimaging Features in Charcot–Marie–Tooth Patients with GNB4 Mutations
- Source :
- Life, Vol 11, Iss 494, p 494 (2021), Life, Volume 11, Issue 6
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the GNB4 gene cause dominant intermediate CMT type F (CMTDIF). The aim of this study is to investigate phenotypic heterogeneities and characteristics of CMT patients with GNB4 mutations. We enrolled 1143 Korean CMT families and excluded 344 families with a PMP22 duplication. We further analyzed the 799 remaining families to find their GNB4 mutations using whole-exome sequencing (WES). We identified two mutations (p.Gly77Arg and p.Lys89Glu) in three families, among which a heterozygous p.Gly77Arg mutation was novel. In addition, a significant uncertain variant (p.Thr177Asn) was observed in one family. The frequency of the GNB4 mutation in the Korean population is 0.38% in PMP22 duplication-negative families. All three families showed de novo mutation. Electrophysiological findings regarding the p.Lys89Glu mutation showed that the motor nerve conduction velocity (MNCV) of the median nerve was markedly reduced, indicating demyelinating neuropathy, and sural nerve biopsy revealed severe loss of myelinated axons with onion bulb formation. Lower extremity Magnetic Resonance Imaging (MRI) demonstrated relatively more severe intramuscular fat infiltrations in demyelinating type (p.Lys89Glu mutation) patients compared to intermediate type (p.Gly77Arg mutation) patients. The anterolateral and superficial posterior compartment muscles of the distal calf were preferentially affected in demyelinating type patients. Therefore, it seems that the investigated GNB4 mutations do cause not only the known intermediate type but also demyelinating-type neuropathy. We first presented three Korean families with GNB4 mutations and found phenotypic heterogeneities of both intermediate and demyelinating neuropathy. We suggest that those findings are useful for the differential diagnosis of CMT patients with unknown GNB4 variants.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
peripheral neuropathy
Science
Charcot–Marie–Tooth disease
medicine.disease_cause
General Biochemistry, Genetics and Molecular Biology
Article
CMTDIF
03 medical and health sciences
GNB4
0302 clinical medicine
Gene duplication
medicine
Ecology, Evolution, Behavior and Systematics
Mutation
neuroimaging
medicine.diagnostic_test
business.industry
Paleontology
Magnetic resonance imaging
medicine.disease
Phenotype
Median nerve
030104 developmental biology
Peripheral neuropathy
Space and Planetary Science
Differential diagnosis
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20751729
- Volume :
- 11
- Issue :
- 494
- Database :
- OpenAIRE
- Journal :
- Life
- Accession number :
- edsair.doi.dedup.....6511c2da653de867abde5eae2a395a3b