Characterization of a Portuguese family with Charcot-Marie-Tooth disease type 1E due to a novel point mutation in the PMP22 gene

Copyright © 2021 Elsevier B.V. All rights reserved..

INTRODUCTION: Point mutations in the Peripheral Myelin Protein 22 (PMP22) gene comprise less than 5% of the Charcot-Marie-Tooth (CMT) type 1 cases, and individualize either the CMT 1E subtype, or Hereditary Neuropathy with Liability to Pressure Palsy. The phenotype of CMT 1E presents with a severe early-onset polyneuropathy associated with deafness, although the clinical spectrum is broad.

CASE REPORT: We describe a novel PMP22 gene point mutation (c.84G>T;p.(Trp28Cys)) in three patients of a Portuguese family with variable phenotypes, ranging from asymptomatic to mild complaints of distal limb numbness and gait difficulties, with the age of onset of symptoms ranging from mid-twenties to late-sixties, and no associated disability. In all affected patients, there was evidence of diffuse demyelinating sensorimotor polyneuropathy. Hearing loss does not seem to be associated with this variant, albeit neuropathic pain was reported.

CONCLUSIONS: These findings suggest that this particular point mutation in the PMP22 gene is associated with a mild phenotype, further emphasizing that there are still unknown mechanisms (genetic and/or epigenetic) that may play a role in the clinical spectrum of CMT1E patients. Next generation sequencing panels including commonly mutated genes in CMT should be considered in CMT1 cases negative for PMP22 gene duplication.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:208

Enthalten in:

Clinical neurology and neurosurgery - 208(2021) vom: 24. Sept., Seite 106829

Sprache:

Englisch

Beteiligte Personen:

Fernandes, Marco [VerfasserIn]
Caetano, André [VerfasserIn]
Castelhano, Luís [VerfasserIn]
Santos, Luís [VerfasserIn]

Links:

Volltext

Themen:

CMT 1E
Case Reports
Demyelinating neuropathy
Inherited neuropathy
Journal Article
Myelin Proteins
PMP22
PMP22 protein, human
Point mutation

Anmerkungen:

Date Completed 25.01.2022

Date Revised 25.01.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.clineuro.2021.106829

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM328768464