Case reportA novel MPZ mutation in Charcot–Marie–Tooth disease type 1B with focally folded myelin and multiple entrapment neuropathies
Introduction
Charcot–Marie–Tooth (CMT) disease is the most common inherited peripheral neuropathy and is both clinically and genetically heterogeneous. CMT type 1B (CMT1B) disease is an autosomal dominant demyelinating neuropathy caused by point mutations in the myelin protein zero (MPZ) gene that encodes the major structural component of peripheral myelin [1]. Most individuals with CMT1B develop one of two phenotypes: an early (childhood) onset neuropathy with very slow nerve conduction velocities (NCV) and predominantly demyelination on nerve biopsy, or a late (adult) onset neuropathy with minimal to moderately slowed NCV and predominant axonal neuropathy on nerve biopsy [1], [2]. Among the demyelination types, some mutations in MPZ were associated with myelin uncompaction, and a few were associated with focal foldings of the myelin sheath without any obvious relation to the molecular lesion [1], [3], [4], [5], [6], [7], [8], [9]. So far, more than 120 distinct mutations have been identified in MPZ, comprising missense and frameshift mutations or small deletions (see http://www.molgen.ua.ac.be/CMTMutations/default.cfm). Here we describe a CMT1B patient with an AAC→AGC transition in MPZ, encoding a novel Asn131Ser mutation, who exhibited focally folded myelin sheaths in a sural nerve biopsy. She underwent bilateral carpal tunnel and tarsal tunnel release 5 years before being diagnosed with CMT, which provided transient relief from the symptoms and improvements in nerve conduction parameters.
Section snippets
Case report
The patient is a 49-year-old female with a body mass index of 19.6. Her developmental motor milestones were almost normal. When she was an elementary school student, she could not run as fast as other classmates. At the age of 38, she noticed progressive weakness, dysesthesias, and wasting of upper extremities. At the age of 39 she presented with dysesthesias of the soles and consulted an orthopedic department. Nerve conduction velocities (NCV) were markedly reduced when she was 44. In the
Discussion
We present a 49-year-old woman suffering from motor and sensory polyneuropathy with the onset of symptoms during the first decade of life. She underwent carpal and tarsal tunnel decompression of both hands and feet, yielding temporary relief from the dysesthesias and improvements in nerve conduction parameters. At the time of her referral to the Neurology department, she exhibited moderate weakness and atrophy of the hand muscles, as well as an impairment of all sensory modalities in the upper
Acknowledgement
This work was supported by grants from the Ministry of Health, Labor and Welfare and the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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