Abstract Details

Charcot-Marie-Tooth diseases (CMT) are a group of inherited peripheral nerve disorders clinically characterized by sensory loss, muscle weakness and atrophy in distal limbs. CMT is classified into dys-/de-myelinating and axonal types based on nerve conduction studies (NCS) with reduced conduction velocities (CV) in the former (type-I) but normal or minimally decreased CV in the latter (type-II). Recessive mutations in IGHMBP2 have been reported to cause the axonal CMT (CMT2S).

We report a family with compound mutations in IGHMBP2 gene that manifests a novel phenotype.

A family with six members will be evaluated after the proband was studied by neurological examination, DNA testing, and NCS.

This is a 40-year-old woman with a chief complaint of chronic progressive sensory loss and weakness in distal limbs since her toddler. Currently, she uses ankle orthosis for gait instability and has impaired hand dexterity. Her younger brother reportedly manifests a similar phenotype. On Neurological examination, there was limb muscle atrophy below her elbows and knees. Deep tendon reflexes were absent in the legs. NCS demonstrated that CVs ranged from 32.6 m/s to 36.8 m/s. DNA testing showed three heterozygous variants in IGHMBP2: Atg971Glufs*4 frame-shift mutation (known pathogenic), Arg730Trp, and Glu376Lys. Additional DNA samples from other family members will be analyzed to determine whether the two missense mutations are on different allele from the allele with Atg971Glufs*4 and fibroblasts from skin biopsies of the family will be tested for the level of IGHMBP2 protein.

Here we have identified a family with a demyelinating polyneuropathy and its associated compound mutations in IGHMBP2. This finding expands the genotypic and phenotypic spectrums of the diseases.