1.Novel Compound Heterozygous Nonsense PRX Mutations in a Korean Dejerine-Sottas Neuropathy Family.
Ye Ji CHOI ; Young Se HYUN ; Soo Hyun NAM ; Heasoo KOO ; Young Bin HONG ; Ki Wha CHUNG ; Byung Ok CHOI
Journal of Clinical Neurology 2015;11(1):92-96
BACKGROUND: Mutations in the gene encoding periaxin (PRX) are known to cause autosomal recessive Dejerine-Sottas neuropathy (DSN) or Charcot-Marie-Tooth disease type 4F. However, there have been no reports describing Korean patients with these mutations. CASE REPORT: We examined a Korean DSN patient with an early-onset, slowly progressive, demyelinating neuropathy with prominent sensory involvement. Whole-exome sequencing and subsequent capillary sequencing revealed novel compound heterozygous nonsense mutations (p.R392X and p.R679X) in PRX. One mutation was transmitted from each of the patient's parents. No unaffected family member had both mutations, and the mutations were not found in healthy controls. CONCLUSIONS: We believe that these novel compound heterozygous nonsense mutations are the underlying cause of DSN. The clinical, electrophysiologic, and pathologic phenotypes in this family were similar to those described previously for patients with PRX mutations. We have identified the first PRX mutation in a Korean patient with DSN.
Capillaries
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Charcot-Marie-Tooth Disease
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Codon, Nonsense
;
Hereditary Sensory and Motor Neuropathy*
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Humans
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Parents
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Peripheral Nerves
;
Phenotype
2.Hereditary Motor and Sensory Neuropathy Type VI with Bilateral Middle Cerebellar Peduncle Involvement.
Jung Hwan OH ; Han Sang LEE ; Dong Min CHA ; Sa Yoon KANG
Experimental Neurobiology 2014;23(3):266-269
Charcot-Marie-Tooth disease (CMT) 2A with optic atrophy is referred to as hereditary motor and sensory neuropathy type VI (HMSN VI) and is caused by mitofusin 2 gene (MFN2) mutation. In patients with MFN2 related CMT, central nervous system is known to be also involved and cerebral white matter is mostly involved. We report a patient confirmed as HMSN VI who had isolated bilateral middle cerebellar peduncular lesions in brain MRI.
Brain
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Central Nervous System
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Charcot-Marie-Tooth Disease
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Hereditary Sensory and Motor Neuropathy*
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Humans
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Magnetic Resonance Imaging
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Mitochondria
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Optic Atrophy
3.Myelin Protein Zero (MPZ) Gene Analysis in Korean Patients with Charcot-Marie-Tooth: Clinical and Electrophysiological Characteristics.
Byung Ok CHOI ; Ki Wha CHUNG ; Hyun Ji CHO ; Kee Duk PARK ; Kwang Soo LEE ; Seung Min KIM ; Il Nam SUNWOO
Journal of the Korean Neurological Association 2005;23(2):227-231
BACKGROUND: Mutations in the myelin protein zero (MPZ) gene, which is located on chromosome 1q21-q22, is present in Charcot-Marie-Tooth disease type 1B (CMT1B), CMT type 2, Dejerine-Sottas syndrome, and congenital hypomyelination neuropathy. It is proposed that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. In this study, we investigated to determine the clinical and electrophysiological characteristics in CMT patients with mutations in the MPZ gene. METHODS: We examined mutations of MPZ, in 62 Korean families diagnosed as having CMT disease. Mutations were confirmed by through both strands sequencing. Nerve conduction studies were carried out in CMT patients having each mutation. RESULTS: The three mutations (Asp118Asn, c.449-1G>T (3'-splice site), Lys236Glu), determined to be novel, were not detected in the 105 healthy controls. The mutation frequency of MPZ was similar as those found in several European populations. Electrophysiologically, 3'-splice site mutation (449-1G>T) showed the conduction block and moderate slowing nerve conduction velocities like that of CMT1B. However, the other mutations represented the electrophysiological features of CMT type 2. CONCLUSIONS: We report the identified three novel MPZ mutations in Korean CMT patients and the phenotype-genotype correlations based on nerve conduction studies.
Axons
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Charcot-Marie-Tooth Disease
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Hereditary Sensory and Motor Neuropathy
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Humans
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Mutation Rate
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Myelin P0 Protein*
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Myelin Sheath*
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Neural Conduction
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Phenotype
4.Mutational Analysis of the Neurofilament Light Chain (NEFL) Gene in Patients with Charcot-Marie-Tooth Disease.
Hyun Ji CHO ; Ki Wha CHUNG ; Il Nam SUNWOO ; Kee Duk PARK ; Dae Sung KIM ; Bum Chun SEO ; Mi Sun LEE ; Eun Kyoung YOUN ; Byung Ok CHOI
Journal of the Korean Neurological Association 2005;23(5):642-649
BACKGROUND: Charcot-Marie-Tooth (CMT) disease is the most common form of inherited motor and sensory neuropathy. Neurofilament light chain polypeptide (NEFL) is one of the most abundant cytoskeletal components of the neuron. The NEFL gene encoding the neurofilament light chain plays an important role in the axonal structure that includes an extensive fibrous network in the cytoplasm of the neuron. Mutations in the NEFL gene are also present in CMT2E, CMT type 1 and Dejerine-Sottas syndrome. However, there have been no reports to investigate the NEFL genes in Korean CMT patients. Therefore, we investigated to find the clinical characteristics in patients with the NEFL gene mutation. METHODS: We examined mutations of the NEFL gene in 125 Korean CMT families. Mutations were confirmed by the sequencing of both strands. Nerve conduction studies were carried out on CMT patients having each mutation. RESULTS: Three pathogenic mutations were found in 3 families, and 2 polymorphisms in 2 families. Two mutations (Leu334Pro, Pro22Arg) were determined too novel, and those were not detected in 105 healthy controls. A de novo missense mutation was found in a CMT family with the NEFL mutation. The frequency of the NEFL mutation was 2.4%, which was similar in Europeans, and lower than those found in Japanese. Pro22Arg and Glu397Lys mutations showed demyelinating neuropathy and Leu334pro mutation showed axonal neuropathy. CONCLUSIONS: We found NEFL mutations in patients with sporadic or dominantly inherited CMT. NEFL mutations should be considered in the evaluation of CMT or related neuropathies with various clinical features.
Asian Continental Ancestry Group
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Axons
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Charcot-Marie-Tooth Disease*
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Cytoplasm
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Hereditary Sensory and Motor Neuropathy
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Humans
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Mutation, Missense
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Neural Conduction
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Neurons
5.Current Issues of the Charcot-Marie-Tooth Disease.
Journal of the Korean Medical Association 2007;50(5):457-463
Hereditary motor and sensory neuropathy (HMSN), or Charcot-Marie-Tooth (CMT) disease, was described by Charcot and Marie in France and, independently, by Tooth in England in 1886. CMT is the most common form of inherited motor and sensory neuropathy, and is a genetically heterogeneous group of disorders in the peripheral nervous system. Traditionally, CMT has been subclassified into autosomal dominant inherited demyelinating (CMT1) and axonal (CMT2) neuropathies, X-linked neuropathy (CMTX), and autosomal recessive inherited neuropathy (CMT4). There are several related peripheral neuropathies, such as Dejerine-Sottas neuropathy (DSN), congenital hypomyelination neuropathy (CHN), hereditary neuropathy with liability to pressure palsies (HNPP), and giant axonal neuropathy (GAN). A large amount of new information on the genetic causes of CMT has become available, and mutations causing the disease have been associated with more than 20 different genes and 40 chromosomal loci. Advances in our understanding of the molecular basis of CMT have revealed an enormous diversity in genetic mechanisms, despite the clinical entity that is relatively uniform at presentation. Recent studies have shown therapeutic effects of certain chemicals in animal models of CMT1A, which suggests potential therapies for the most common form of CMT, CMT1A. This review focuses on the subgroups of inherited motor and sensory neuropathy on which there has been an explosion of new molecular genetic information over the past decade.
Axons
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Charcot-Marie-Tooth Disease*
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England
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Explosions
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France
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Giant Axonal Neuropathy
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Hereditary Sensory and Motor Neuropathy
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Models, Animal
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Molecular Biology
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Paralysis
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Peripheral Nervous System
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Peripheral Nervous System Diseases
;
Tooth
6.Delayed Recovery of Neuromuscular Blockade by Rocuronium in a Patient with Charcot-Marie-Tooth Disease: Case reports.
Yong Kwan CHEONG ; Cheol LEE ; Yong SON ; Yoon Kang SONG ; Tai Yo KIM ; Dea Jung KIM ; Seri O
Korean Journal of Anesthesiology 2007;53(1):145-149
Charcot-Marie-Tooth disease, which is also known as hereditary motor and sensory neuropathy, is a heterogenous group of inherited diseases of the peripheral nerve. The spectrum of severity varies from asymptomatic individuals to those with severe limb abnormalities requiring corrective surgery. We report two brothers who had previously been diagnosed with Charcot-Marie- Tooth disease 3 years earlier and were scheduled to undergo a correction osteotomy of both feet under general anesthesia. General anesthesia was induced with propofol 2 mg/kg, rocuronium 0.8 mg/kg and was maintained with O2-N2O-Sevoflurane. The younger brother showed no delay in recovery of the neuromuscular blockade but the elder brother showed a delay.
Anesthesia, General
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Charcot-Marie-Tooth Disease*
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Extremities
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Foot
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Hereditary Sensory and Motor Neuropathy
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Humans
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Neuromuscular Blockade*
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Osteotomy
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Peripheral Nerves
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Propofol
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Siblings
;
Tooth Diseases
7.DNA diagnostic testing in hereditary motor and sensory neuropathies.
Journal of Genetic Medicine 2007;4(2):115-121
Hereditary motor and sensory neuropathy (HMSN; Charcot-Marie-Tooth disease, CMT) was first described by Charcot and Marie in France and, independently, by Tooth in England in 1886. HMSN is the most common form of inherited motor and sensory neuropathy, and is a genetically heterogeneous disorder of the peripheral nervous system. Using positional cloning methods, the chromosomal localization (locus) of more than 40 inherited peripheral neuropathies was found in the last 15 years. However, these genetic analyses also show that many entities do not show linkage to the known loci. This issue deals with a clinical survey of inherited peripheral neuropathies regarding diagnostic approaches based on the molecular findings.
Charcot-Marie-Tooth Disease
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Clone Cells
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Cloning, Organism
;
Diagnosis
;
Diagnostic Tests, Routine*
;
DNA*
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England
;
France
;
Hereditary Sensory and Motor Neuropathy*
;
Peripheral Nervous System
;
Peripheral Nervous System Diseases
;
Tooth
8.X-linked Charcot-Marie-Tooth Patient with a Novel Cys168Arg Missense Mutation in the Connexin32 Gene.
Byung Ok CHOI ; Il Nam SUNWOO ; Kee Duk PARK ; Yong Jae KIM ; Kyoung Gyu CHOI ; Mi Sun LEE ; Jung Hee HWANG ; Ki Wha CHUNG
Journal of the Korean Neurological Association 2004;22(1):76-79
X-linked Charcot-Marie-Tooth (CMTX) disease is a clinically heterogeneous hereditary motor and sensory neuropathy. The X-linked inheritance showed an absence of male-to-male transmission and a more severe disease phenotype in affected males compared to that in affected female. A missense mutation, Cys168Arg, was found in connexin 32 gene (Cx32/GJB1) from a patient with CMTX neuropathy. The familial history of this patient also suggested that the disease is X-linked CMT. Thus, we report a CMTX family having the novel Cys168Arg mutation in the Cx32 gene.
Female
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Genes, X-Linked
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Hereditary Sensory and Motor Neuropathy
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Humans
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Male
;
Mutation, Missense*
;
Phenotype
9.Hereditary motor neuropathy - a family with 9 cases.
Jing CHEN ; Ran AN ; Yan-ming XU
Chinese Journal of Medical Genetics 2013;30(5):607-607
Adult
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Aged
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Female
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Hereditary Sensory and Motor Neuropathy
;
diagnosis
;
genetics
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Humans
;
Male
;
Middle Aged
;
Pedigree
10.Hereditary Motor and Sensory Neuropathy Type I: A case report
Han Koo LEE ; Dae Kyung BAE ; Myung Ho KIM ; Byoung Wan AHN
The Journal of the Korean Orthopaedic Association 1978;13(2):225-231
Hereditary motor and sensory neuropathy is an unusual disease which is characterized by deformity of phe foot, acral sensory loss, decreare of deep tendon reflexes, enlargement of peripheral nerve and diminished motor conduction velocity. We report a case of hereditary motor and sensory neuropathy type I.
Congenital Abnormalities
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Foot
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Hereditary Sensory and Motor Neuropathy
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Peripheral Nerves
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Reflex, Stretch