Charcot Marie Tooth disease type 4J with complex central nervous system features

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Charcot Marie Tooth disease (CMT4J) is a peripheral neuropathy.
• Most CMT4J patients lack central nervous system (CNS) deficits.

Purpose of the Study:

• To investigate the genetic basis of CMT4J with additional CNS symptoms in a family.
• To explore the functional impact of identified genetic variants.

Main Methods:

• Genetic testing to identify variants in the FIG4 gene.
• Western blot analysis to assess FIG4 protein levels in patient fibroblasts.
• RT-PCR to evaluate exon skipping.

Main Results:

• Identified two FIG4 variants: c.122T>C (p.I41T) and an intronic variant (c.1949-10T>G).
• Proband fibroblasts exhibited absent FIG4 protein and exon 18 skipping.
• The common p.I41T variant and the intronic variant were found together.

Conclusions:

• The combined effect of the p.I41T and intronic variants likely causes loss of FIG4 protein function.
• This loss of function is postulated to be responsible for the CNS manifestations in the family.
• Suggests a potential genotype-phenotype correlation for FIG4 mutations in CMT4J.