Abstract
Myelin protein zero (MPZ) is a major component of compact myelin in peripheral nerves. Mutations in MPZ have been associated with different Charcot–Marie–Tooth disease (CMT) phenotypes (CMT1B, CMT2I/J, CMTDI), Dejerine–Sottas syndrome, and congenital hypomyelination neuropathy. Here, we report phenotypic variability in a four-generation Chinese family with the MPZ mutation Asp121Asn. Genetic testing was performed on nine family members and 200 controls. Clinical, electrophysiological and skeletal muscle MRI assessments were available for review in six family members. A novel heterozygous missense mutation, Asp121Asn, was observed in five affected members of the family. Unaffected relatives and 200 normal controls were without the mutation. Four of the affected members of the family displayed late-onset, predominantly axonal sensory and motor neuropathy, pupil abnormalities, and progressive sensorineural hearing loss. One young affected member presented with Argyll–Robertson pupils and diminished deep tendon reflexes in the lower limbs. The MPZ mutation Asp121Asn may be associated with late-onset axonal neuropathy, early onset hearing loss and pupil abnormalities. Our report expands the number and phenotypic spectrum of MPZ mutations.
Highlights
Charcot–Marie–Tooth disease (CMT) is a genetically heterogeneous group of disorders affecting the peripheral nervous system
Patients with Myelin protein zero (MPZ) mutations exhibit a wide range of phenotypic variability beyond the peripheral nervous system, including pupillary abnormalities, hearing loss, diaphragmatic weakness or chronic cough, restless-leg-like symptoms and multiple sclerosis
We described a large Chinese family with late-onset axonal neuropathy, pupil abnormalities, and hearing loss associated with a novel mutation in MPZ
Summary
Charcot–Marie–Tooth disease (CMT) is a genetically heterogeneous group of disorders affecting the peripheral nervous system. The number of disease genes identified in CMT has expanded rapidly over the past few decades (Rossor et al, 2013). Mutations in the myelin protein zero (MPZ) gene are one of the most frequent causes of CMT. We present five patients from a four-generation Chinese family who contain a novel missense mutation in MPZ. The family included 7 affected and 10 unaffected members over four generations (Figure 1A). This study was approved by the ethical committees of the China-Japan Friendship Hospital and the Peking University Third Hospital. Written informed consent was obtained from all participants
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