Dysmyelinating and demyelinating Charcot–Marie–Tooth disease associated with two myelin protein zero gene mutations

Drac, Hanna; Kabzińska, Dagmara; Moszyńska, Izabela; Strugalska-Cynowska, Halina; Hausmanowa-Pétrusewicz, I; Kochański, Andrzej

doi:10.1007/s13353-010-0003-3

Cited by 7 publications

(5 citation statements)

References 15 publications

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“…It was found that a similar amino acid substitution at codon 132 (p. Pro132Leu) resulted in the focally folded myelin with degenerative changes. 31 Mutations in positions close to those described in this current case report were found in ClinVar and patients carrying these pathogenic variants had similar symptoms to those identified in the proband with the novel p.Pro133Leu substitution. A previous study described the p.Asn131Lys mutation in exon 3 of the MPZ gene, which is responsible for its adhesive properties.…”

Section: Discussionsupporting

confidence: 74%

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Novel mutation in the MPZ gene causes early-onset but slow-progressive Charcot–Marie–Tooth disease in a Russian family: a case report

Kozina

Барышникова

Ilinskaya³

et al. 2022

J Int Med Res

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Charcot–Marie–Tooth disease (CMT) is a genetically heterogeneous group of peripheral neuropathies most of which are associated with mutations in four genes including peripheral myelin protein-22 ( PMP22), myelin protein zero ( MPZ), gap junction protein beta1 ( GJB1) and mitofusin2 ( MFN2). This current case report describes the clinical and genetic characteristics of a 6-year-old male proband. A physical examination revealed muscular hypotonia. He started walking on his own at 18 months. A nerve conduction study with needle electromyography revealed conduction block. A novel MPZ mutation (c.398C > T, p.Pro133Leu) was revealed in the proband. This mutation was also found in the 32-year-old father of the proband. The father had had deformity of the feet and distal muscle weakness since childhood. The novel p.Pro133Leu pathogenic mutation was responsible for early onset but slowly progressive CMT1B. We assume that this site is an intolerant to change region in the MPZ gene. This variant in the MPZ gene is an important contributor to hereditary neuropathy with reduced nerve conduction velocity in the Russian population. This case highlights the importance of whole exome sequencing for a proper clinical diagnosis of CMT associated with a mutation in the MPZ gene.

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Section: Discussionsupporting

confidence: 74%

“…It was found that a similar amino acid substitution at codon 132 (p.Pro132Leu) resulted in the focally folded myelin with degenerative changes. 31 …”

Section: Discussionmentioning

confidence: 99%

Novel mutation in the MPZ gene causes early-onset but slow-progressive Charcot–Marie–Tooth disease in a Russian family: a case report

Kozina

Барышникова

Ilinskaya³

et al. 2022

J Int Med Res

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“…The cumulative effect of two mild variants was hypothesized in a CMT family with simultaneous MFN2 and GDAP1 variants 24 . To the best of our knowledge, there have been a few compound heterozygous variants of MPZ 25‐27 . Regarding the compound heterozygous variant in our study, this patient was classified as demyelinating CMT.…”

Section: Discussionmentioning

confidence: 76%

Genetic spectrum of Charcot–Marie–Tooth disease associated with myelin protein zero gene variants in Japan

et al. 2020

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We aimed to reveal the genetic features associated with MPZ variants in Japan. From April 2007 to August 2017, 64 patients with 23 reported MPZ variants and 21 patients with 17 novel MPZ variants were investigated retrospectively. Variation in MPZ variants and the pathogenicity of novel variants was examined according to the American College of Medical Genetics standards and guidelines. Age of onset, cranial nerve involvement, serum creatine kinase (CK), and cerebrospinal fluid (CSF) protein were also analyzed. We identified 64 CMT patients with reported MPZ variants. The common variants observed in Japan were different from those observed in other countries. We identified 11 novel pathogenic variants from 13 patients. Six novel MPZ variants in eight patients were classified as likely benign or uncertain significance. Cranial nerve involvement was confirmed in 20 patients. Of 30 patients in whom serum CK levels were evaluated, eight had elevated levels. Most of the patients had age of onset >20 years. In another subset of 30 patients, 18 had elevated CSF protein levels; four of these patients had spinal diseases and two had enlarged nerve root or cauda equina. Our results suggest genetic diversity across patients with MPZ variants.

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“…Two mutations in the MPZ Gene (His81Tyr and Val113Phe) were report in a 45-year-old female with a peripheral neuropathy with demyelinating and axonal features, pes cavus and pupillary light-near dissociation with a less severe phenotype in comparison to a patient with single His81 Arg mutation [ 31 ]. In a study carried in the Polish population, Drac et al [ 32 ] described two CMT families in which the Ile135Thr and Pro132Leu mutations for the gene MPZ were identified. In the family carrying the Pro132Leu mutations, the sural nerve biopsy displayed hypomyelination-dysmyelination process.…”

Section: Discussionmentioning

confidence: 99%

Concomitant MPZ and MFN2 Gene Variants and Charcot Marie Tooth Disease in a Boy: Clinical and Genetic Analysis—Literature Review

Comella

Collotta

Pavone

et al. 2022

Case Reports in Pediatrics

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Charcot- Marie- Tooth (CMT) disease includes a group of clinically and genetically heterogeneous neuropathic disorders with an estimated frequency of 1 on 2.500 individuals. CMTs are differently classified according to the age of onset, type of inheritance, and type of inheritance plus clinical features. For these disorders, more than 100 genes have been implicated as causal factors, with mutations in the PMP22 being one of the most common. The demyelinating type (CMT1) affects more than 30% of the CMTs patients and manifests with motor and sensory dysfunctions of the peripheral nervous system mainly starting with slow progressive weakness of the lower extremities. We report here a 12 year- old boy presenting with typical features of CMT1 type, hearing impairment, and inguinal hernia who at the next-generation sequence analysis displayed a concomitant presence of two variants: the c.233 C>T p.Ser 78Leu of the MPZ gene (NM_000530.6) characterized as pathogenetic and the c.1403 G>A p.Arg 468His of the MFN2 gene (NM_014874.3) characterized as VUS. Concomitant variant mutations in CMTs have been uncommonly reported. The role of these gene mutations on the clinical expression and a literature review on this topic is discussed.

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Dysmyelinating and demyelinating Charcot–Marie–Tooth disease associated with two myelin protein zero gene mutations

Cited by 7 publications

References 15 publications

Novel mutation in the MPZ gene causes early-onset but slow-progressive Charcot–Marie–Tooth disease in a Russian family: a case report

Novel mutation in the MPZ gene causes early-onset but slow-progressive Charcot–Marie–Tooth disease in a Russian family: a case report

Genetic spectrum of Charcot–Marie–Tooth disease associated with myelin protein zero gene variants in Japan

Concomitant MPZ and MFN2 Gene Variants and Charcot Marie Tooth Disease in a Boy: Clinical and Genetic Analysis—Literature Review

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