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Published on: April 4, 2018
A novel stop codon mutation in the PMP22 gene associated with a variable phenotype
K T Abe1, A M M Lino, M T A Hirata
1Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matao 277 CEP, São Paulo 05508-900, Brazil.
Abstract:
The most frequent inherited peripheral neuropathy is the peripheral myelin protein 22 (PMP22) gene related disease. Duplication, deletion, and point mutations in that gene are associated with phenotypic variability. Here we report a family carrying a novel mutation in the PMP22 gene (c. 327C>A), which results in a premature stop codon (Cys109stop). The family members who carry this mutation have a Charcot-Marie-Tooth type 1 variable phenotype, ranging from asymptomatic to severely affected. These findings suggest that the fourth transmembrane domain of the PMP22 gene may play an important role, although the intrafamilial clinical variability reinforces the observation that pathogenic mutations are not always phenotype determinant and that other factors (genetic or epigenetic) modulate the severity of the clinical course.
Insights
A novel mutation in the peripheral myelin protein 22 (PMP22) gene causes Charcot-Marie-Tooth type 1 disease with variable symptoms. This suggests other factors influence disease severity beyond the PMP22 mutation itself.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Inherited peripheral neuropathies are common, with peripheral myelin protein 22 (PMP22) gene mutations being the most frequent cause.
- PMP22 gene alterations, including duplications, deletions, and point mutations, lead to diverse clinical presentations.
Purpose of the Study:
- To investigate a family with a novel mutation in the PMP22 gene.
- To understand the relationship between this specific PMP22 mutation and the resulting phenotype.
Main Methods:
- Genetic sequencing to identify mutations in the PMP22 gene.
- Clinical evaluation of family members carrying the mutation.
Main Results:
- Identification of a novel PMP22 gene mutation (c. 327C>A) causing a premature stop codon (Cys109stop).
- Family members with this mutation exhibited a variable Charcot-Marie-Tooth type 1 phenotype, from asymptomatic to severe.
- The fourth transmembrane domain of PMP22 appears functionally significant.
Conclusions:
- The novel PMP22 mutation leads to a variable Charcot-Marie-Tooth type 1 phenotype.
- Clinical variability highlights that mutations are not always deterministic; genetic or epigenetic factors modulate disease severity.
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