Severe Charcot-Marie-Tooth neuropathy type 1A with 1-base pair deletion and frameshift mutation in the peripheral myelin protein 22 gene

Ionâşescu, Victor; Searby, Charles; Ionasescu, Rebecca; Reisin, Ricardo; Ruggieri, Víctor Luis; Arberas, Claudia

doi:10.1002/(sici)1097-4598(199710)20:10<1308::aid-mus14>3.0.co;2-z

Cited by 20 publications

(11 citation statements)

References 19 publications

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“…In contrast to our patient, in the two other patients, there was slowing down of motor nerve conduction velocities of n. medianus and n. ulnaris (not measurable in our patient) and cranial nerve involvement. The male patient described by Ionasescu et al (11) also suffered from scoliosis, which required surgical intervention, and the female patient described by Boerkoel et al (12) showed the same foot deformity as our patient. Unfortunately, no description of the patient's feet was included in the paper by Ionasescu et al (11).…”

Section: Discussionsupporting

confidence: 77%

“…Since 1991, when the first mutation involving the PMP22 gene was found to be a duplication (10), more than 50 distinct sequence variations have been described in which most missense mutations result in a more severe neuropathy than that associated with the PMP22 duplication (CMT1A) (4). Ionasescu et al (11) and Boerkoel et al (12) reported two patients in whom the same 1-bp deletion within codon 94 of the PMP22 gene was identified (c.281delG), as in our patient ( Table 1). Onset of polyneuropathy in all three patients was described starting in the first years of life, and they all had distal severe motor involvement.…”

Section: Discussionsupporting

confidence: 73%

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Severe phenotype with cis‐acting heterozygous PMP22 mutations

et al. 2009

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We report on a 20-year-old male with severe Charcot-Marie-Tooth (CMT) disease and a de novo deletion (c.281delG, p.G94AfsX17) on the paternal PMP22 allele harboring c.353C>T (p.T118M). RNA-based sequence analysis confirmed the absence of nonsense-mediated decay and the presence of the mutant transcripts in Epstein-Barr virus-transformed lymphoblastoid cells of our patient. His clinical findings included early onset of polyneuropathy, loss of muscle mass with distal pareses, hammer toes, and progressive scoliosis. There was no neuropsychological alteration. Our results suggest that the deletion c.281delG alone is responsible for the severe CMT phenotype. To the best of our knowledge, this is the second report on a proven paternal origin of a de novo single-base mutation in the PMP22 gene.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 73%

Severe phenotype with cis‐acting heterozygous PMP22 mutations

et al. 2009

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“…The primary genetic cause of CMT1A is a duplication of PMP22 resulting from the unequal crossover between two homologous repetitive elements that flank a 1.4-Mb region of chromosome 17p12 65 . Importantly, PMP22 frame-shift 66 and loss of function point mutations 67 have been found in severely affected CMT1A patients; likewise, same loss of function point mutations in Pmp22 were found in the Trembler-J mouse, a CMT1A model 68 . The reciprocal deletion of PMP22 is associated with non-progressive hereditary neuropathy with liability to pressure palsies (HNPP) 69 .…”

Section: Reciprocal Cnvs and Single-gene Defectsmentioning

confidence: 67%

Genetic architecture of reciprocal CNVs

Golzio

Katsanis

2013

Current Opinion in Genetics & Development

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Copy number variants (CNVs) represent a frequent type of lesion in human genetic disorders that typically affects numerous genes simultaneously. This has raised the challenge of understanding which genes within a CNV drive clinical phenotypes. Although CNVs can arise by multiple mechanisms, a subset is driven by local genomic architecture permissive to recombination events that can lead to both deletions and duplications. Phenotypic analyses of patients with such reciprocal CNVs have revealed instances in which the phenotype is either identical or mirrored; strikingly, molecular studies have revealed that such phenotypes are often driven by reciprocal dosage defects of the same transcript. Here we explore how these observations can help the dissection of CNVs and inform the genetic architecture of CNV-induced disorders.

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“…We noted a complete absence of myelin in a peripheral nerve biopsy taken from their son, which is further support for an underexpression of PMP22 in the two parents. Ionasescu et al 20 reported a similar case, except that their patient had a deletion and a frameshift mutation in the PMP22 gene.…”

Section: Discussionmentioning

confidence: 87%

Ultrastructural Immunocytochemical Abnormalities of Peripheral Myelin Proteins in Hereditary Sensory‐Motor Neuropathies: 12 cases

Anani¹,

Sindou²,

Richard³

et al. 1999

Annals of the New York Academy of Sciences

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Hereditary sensorimotor neuropathies form a heterogeneous group of genetically determined diseases, of which Charcot-Marie-Tooth (CMT) disease is the most common. In order to establish relations between genotype and the expression of peripheral myelin proteins, we carried out a quantitative study by ultrastructural immunocytochemistry of several myelin proteins (PMP22, P0, MBP) on sural nerve biopsy samples from 12 unrelated CMT patients. The diagnosis of CMT was based on the clinical, electrophysiological, and histological findings along with those of molecular biological studies. CMT X diagnoses were not included in this study. The expression of myelin proteins was well correlated with the molecular biological findings in these patients. The results also provided evidence for interference between different myelin proteins. Our findings are in line with the results from animal studies (trembler and knock-out mice), which may provide insights into the pathogenesis of these human conditions.

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Severe Charcot-Marie-Tooth neuropathy type 1A with 1-base pair deletion and frameshift mutation in the peripheral myelin protein 22 gene

Cited by 20 publications

References 19 publications

Severe phenotype with cis‐acting heterozygous PMP22 mutations

Severe phenotype with cis‐acting heterozygous PMP22 mutations

Genetic architecture of reciprocal CNVs

Ultrastructural Immunocytochemical Abnormalities of Peripheral Myelin Proteins in Hereditary Sensory‐Motor Neuropathies: 12 cases

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