The molecular dissection of cellular functions of the related gene products has only begun and detailed pathophysiological models are still missing, but already the biological scope of genes linked to CMT2 is more diversified than CMT1.
Charcot-Marie-Tooth disease (CMT), or hereditary motor and sensory neuropathy (HMSN), includes two main subtypes of CMT1/HMSN I (demyelinating), and CMT2/HMSN II (axonal).
Most MPZ mutations lead to the HMSN type I phenotype, with recent reports of Déjérine-Sottas, congenital hypomyelination, and HMSN II also ascribed to MPZ mutations.
The MPZ gene Ser44Phe mutation found in the HMSN II family presented in this study suggests that genetic analysis of HMSN II families should also include the MPZ gene, previously not considered to be involved in the axonal form of HMSN.
The distal HMN shows similarities with the hereditary motor and sensory neuropathies type I and II (HMSN I and HMSN II) or Charcot-Marie-Tooth disease type 1 and 2 (CMT 1 and CMT 2) and with some proximal HMN or spinal muscular atrophies (SMA).
Arthropathy-related pain in a patient with congenital impairment of pain sensation due to hereditary sensory and autonomic neuropathy type II with a rare mutation in the WNK1/HSN2 gene: a case report.
More recently, a different mutation in WNK1 was identified as the cause of hereditary sensory and autonomic neuropathy type II, an early-onset autosomal disease of peripheral sensory nerves.
Mutations in the SLC25A46 gene have been identified in mitochondrial diseases that are sometimes classified as Charcot-Marie-Tooth disease type 2, optic atrophy, and Leigh syndrome.
Mutations in SLC25A46 gene have been identified in mitochondrial diseases that are sometimes classified as Charcot-Marie-Tooth disease type 2, optic atrophy and Leigh syndrome.
Charcot-Marie-Tooth disease type 2 (CMT2) is characterized by a motor conduction velocity of the median nerve of > 38 m/sec and is a genetically heterogeneous disorder with at least three loci identified: CMT2A (1p35-36), CMT2B (3q13-22), CMT2C (not linked to any known loci), and CMT2D (7p14).