Gene dosage effects in hereditary peripheral neuropathy

@article{Gabriel1997GeneDE,
  title={Gene dosage effects in hereditary peripheral neuropathy},
  author={Jean Marc Gabriel and Beat Erne and Davide Pareyson and Angelo Sghirlanzoni and Franco Taroni and Andreas Johann Steck},
  journal={Neurology},
  year={1997},
  volume={49},
  pages={1635 - 1640}
}
A duplication of a 1.5-Megabase genomic region encompassing the gene for the peripheral myelin protein 22 (PMP22) is found on chromosome 17p11.2-12 in Charcot-Marie-Tooth disease type 1A (CMT1A), whereas the reciprocal deletion is associated with hereditary neuropathy with liability to pressure palsies(HNPP). Since most CMT1A patients harbor three copies of the PMP22 gene, and most HNPP patients carry only a single copy, a gene dosage effect has been proposed as a mechanism for both diseases… 
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PMP 22 expression in dermal nerve myelin from patients with CMT 1 A
TLDR
There was no correlation between neurological disabilities and the level of over-expression of PMP22 protein or mRNA in patients with CMT1A, and variability ofPMP22 levels, rather than absolute level, may play an important role in the pathogenesis of C MT1A.
PMP22 expression in dermal nerve myelin from patients with CMT1A.
TLDR
There was no correlation between neurological disabilities and the level of over-expression of PMP22 protein or mRNA in patients with CMT1A, and variability ofPMP22 levels, rather than absolute level, may play an important role in the pathogenesis of C MT1A.
Inherited Neuropathies: From Gene to Disease
Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot‐Marie‐Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating…
Molecular basis of inherited neuropathies.
TLDR
Overexpression or underexpression of peripheral myelin protein of 22 kDa are causative for the most frequent forms of CMT-CMT1A and hereditary neuropathy with liability to pressure palsies--but the mechanisms that lead to incorrect myelin formation and maintenance are still unknown.
Charcot-Marie-Tooth Polyneuropathy: Duplication, Gene Dosage, and Genetic Heterogeneity
  • J. Lupski
  • Biology, Medicine
    Pediatric Research
  • 1999
TLDR
The identification of PMP22 and other genes involved in myelinopathies demonstrate that these diseases represent a spectrum of disorders resulting from defects inMyelin structure, maintenance, and/or formation.
Normal expression of myelin protein zero with frame‐shift mutation correlates with mild phenotype
TLDR
It is demonstrated by quantitative immunohistochemical as well as by Western blot analyses that MPZ expression levels were not reduced in myelin membranes, a finding that is in accordance with the mild phenotype of this patient.
A novel case of concurrent occurrence of demyelinating-polyneuropathy-causing PMP22 duplication and SOX10 gene mutation producing severe hypertrophic neuropathy
TLDR
An 11-year-old boy with extreme hypertrophic neuropathy is described, the first published case on the co-occurrence of CMT1A and WS type 2, which is attributed to the cumulative effect of mutations in both PMP22 and SOX10 genes, responsible for demyelinating neuropathy.
PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies
PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure…
Ultrastructural Immunocytochemical Abnormalities of Peripheral Myelin Proteins in Hereditary Sensory‐Motor Neuropathies: 12 cases
TLDR
A quantitative study by ultrastructural immunocytochemistry of several myelin proteins on sural nerve biopsy samples from 12 unrelated CMT patients provided evidence for interference between different myelin Protein types, in line with the results from animal studies.
Clinical features and molecular genetics of hereditary peripheral neuropathies
TLDR
This review summarises the clinical and molecular genetic features of primary inherited neuropathies and is aimed primarily at clinicians and geneticists.
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References

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TLDR
It is likely that the gene encoding the peripheral myelin protein PMP 22 is at least one of the genes involved since the PMP22 gene maps within the CMT1A duplication, and point mutations within it have been shown to cause a CMT phenotype in humans and comparable neuropathies in rodents.
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TLDR
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