Ylikallio et al. (2013) reported an 18-year-old Finnish girl with early-onset axonal peripheral neuropathy. She had mildly delayed motor development with independent walking at age 1 year. Examination at age 4 years showed generalized hypotonia, thin build with ... Ylikallio et al. (2013) reported an 18-year-old Finnish girl with early-onset axonal peripheral neuropathy. She had mildly delayed motor development with independent walking at age 1 year. Examination at age 4 years showed generalized hypotonia, thin build with small muscle mass, atrophy of the small muscles in the hands and feet, and areflexia. She walked with a broad-based gait and could not walk on her heels. Electrophysiologic studies showed polyneuropathy of the upper and lower limbs, with decreased motor nerve conduction velocities and decreased sensory and motor amplitudes. She also had pes cavus. Sural nerve biopsy showed a decrease in myelinated fibers and nonspecific axonal degeneration; electron microscopic studies showed neurofilament accumulation within axons. She had no cranial nerve involvement and remained active with normal cognition at age 18 years.
In a Finnish girl with autosomal recessive early-onset Charcot-Marie-Tooth disease type 2R, Ylikallio et al. (2013) identified compound heterozygous mutations in the TRIM2 gene (614141.0001 and 614141.0002). The mutations were found by whole-exome sequencing and segregated with the ... In a Finnish girl with autosomal recessive early-onset Charcot-Marie-Tooth disease type 2R, Ylikallio et al. (2013) identified compound heterozygous mutations in the TRIM2 gene (614141.0001 and 614141.0002). The mutations were found by whole-exome sequencing and segregated with the disorder in the family. Study of patient fibroblasts showed significant deficiency of the TRIM2 protein, consistent with a loss of function. Ylikallio et al. (2013) noted that the neurofilament light chain (162280) is a ubiquitination target of TRIM2, and suggested that abnormal axonal accumulation of neurofilaments underlies the disorder. In addition, Trim2-null mice show gait ataxia and neurodegeneration accompanied by axonal swelling and development of neurofilament aggregates, suggestive of impaired axonal transport (Balastik et al., 2008). No TRIM2 mutations were identified in a cohort of 87 patients with early-onset CMT, indicating that mutations in this gene are a rare cause of the disorder.