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KMID : 0381120160380070659
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Genes and Genomics
2016 Volume.38 No. 7 p.659 ~ p.667
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Genotype?phenotype correlation of Charcot-Marie-Tooth type 1E patients with PMP22 mutations
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Kim Jee-Young
Koo Hae-Soo
Park Kee-Duk
Choi Sun-Sung
Yu Jin-Seok
Hong Young-Bin
Chung Ki-Wha
Choi Byung-Ok
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Abstract
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Charcot-Marie-Tooth disease type 1E (CMT1E) is a demyelinating motor and sensory neuropathy with peripheral myelin protein 22 (PMP22) point mutations. The objective of this study was to identify genetic causes and determine genotype?phenotype correlation in two Korean demyelinating CMT patients based on whole exome sequencing (WES), histological examination of distal sural nerve, and magnetic resonance imaging (MRI) of leg. WES revealed two de novo PMP22 mutations in the two demyelinating CMT patients, including one novel p.Leu82Pro (c.245T>A) mutation in one patient and one previously reported p.Ser72Leu (c.215C>T) mutation in the other patient. Both mutation sites were located in the well conserved second transmembrane domain. No control had the same mutations. The affected individual with the novel p.Leu82Pro mutation showed early onset, scoliosis, and sensory ataxia with ability to walk without assistance. Histopathological examination showed severe damage of myelin and axons. No compound muscle action potentials (CMAPs) were evoked in the upper or lower limb nerves. Leg MRIs revealed mild fatty infiltration of the bilateral peronei muscles consistent with clinical manifestations. The patient with the p.Ser72Leu mutation showed developmental delay in infancy. No CMAPs were elicited. However, she was also able to walk without assistance. In spite of markedly severe electrophysiological defects, leg MRIs showed almost normal findings except slight muscle atrophies of the lower legs. Both patients presented similar clinical features including no CMAPs in electrophysiological tests and mild fatty replacement in the lower leg MRI. Therefore, there was a good genotype?phenotype correlation in both cases.
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KEYWORD
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Charcot-Marie-Tooth disease type 1E (CMT1E), Genotype, Phenotype, Peripheral myelin protein 22 (PMP22), Exome
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