Contribution of copy number variations in CMT1X: a retrospective study

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Charcot-Marie-Tooth disease type 1X (CMT1X) is an X-linked dominant peripheral neuropathy.
• Mutations in the Gap Junction B1 (GJB1) gene are the primary cause of CMT1X.
• The role of GJB1 gene deletions in CMT1X pathogenesis remains unclear.

Observation:

• A retrospective study investigated the incidence of GJB1 gene deletions in CMT1X.
• Multiplex ligation-dependent probe amplification and Sanger sequencing were used for analysis.
• A novel GJB1 deletion was identified in a family with a classical CMT1X phenotype.

Findings:

• The identified GJB1 deletion encompassed both coding and regulatory regions of the gene.
• GJB1 deletions are a rare but relevant cause of CMT1X.
• This deletion variant is associated with a typical CMT1X disease presentation.

Implications:

• GJB1 deletions should be considered in the differential diagnosis of CMT1X.
• Genetic testing for GJB1 copy number variations is crucial for patients with suspected CMT1X lacking point mutations.
• This finding aids in understanding the genetic heterogeneity of CMT1X.