Whole genome sequencing reveals novel IGHMBP2 variant leading to unique cryptic splice-site and Charcot-Marie-Tooth phenotype with early onset symptoms.

ABSTRACT:

Background

Rare variants (RV) in immunoglobulin mu-binding protein 2 (IGHMBP2) [OMIM 600502] can cause an autosomal recessive type of Charcot-Marie-Tooth (CMT) disease [OMIM 616155], an inherited peripheral neuropathy. Over 40 different genes are associated with CMT, with different possible inheritance patterns.

Methods and results

An 11-year-old female with motor delays was found to have distal atrophy, weakness, and areflexia without bulbar or sensory findings. Her clinical evaluation was unrevealing. Whole exome sequencing (WES) revealed a maternally inherited IGHMBP2 RV (c.1730T>C) predicted to be pathogenic, but no variant on the other allele was identified. Deletion and duplication analysis was negative. She was referred to the Undiagnosed Disease Network (UDN) for fur

SUBMITTER: Cassini TA 

PROVIDER: S-EPMC6565564 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature