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Neuropathy in a human without the PMP22 gene.

Saporta, Mario Andre and Katona, Istvan and Zhang, Xuebao and Roper, Helen P and McClelland, Louise and Macdonald, Fiona and Brueton, Louise and Blake, Julian and Suter, Ueli and Reilly, Mary M and Shy, Michael E and Li, Jun (2011) Neuropathy in a human without the PMP22 gene. Archives of neurology, 68 (6). pp. 814-21. ISSN 1538-3687. This article is accessible to all HEFT staff and students via NHS Evidence www.evidence.nhs.uk by using their HEFT Athens login IDs

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Official URL: http://archneur.jamanetwork.com/article.aspx?artic...

Abstract

BACKGROUND

Haploinsufficiency of PMP22 causes hereditary neuropathy with liability to pressure palsies. However, the biological functions of the PMP22 protein in humans have largely been unexplored owing to the absence of patients with PMP22-null mutations.

OBJECTIVE

To investigate the function of PMP22 in the peripheral nervous system by studying a boy without the PMP22 gene and mice without the Pmp22 gene.

DESIGN

The clinical and pathological features of a patient with a PMP22 homozygous deletion are compared with those of Pmp22-null mice.

SETTING

Clinical evaluation was performed at tertiary hospitals in the United Kingdom. Molecular diagnosis was performed at the West Midlands Regional Genetics Laboratory. Immunohistochemistry and electron microscopy analyses were conducted at Wayne State University, Detroit, Michigan. Analysis of the Pmp22 +/- and null mice was performed at Vanderbilt University, Nashville, Tennessee.

PARTICIPANT

A 7-year-old boy without the PMP22 gene.

RESULTS

Motor and sensory deficits in the proband were nonlength-dependent. Weakness was found in cranial muscles but not in the limbs. Large fiber sensory modalities were profoundly abnormal, which started prior to the maturation of myelin. This is in line with the temporal pattern of PMP22 expression predominantly in cranial motor neurons and dorsal root ganglia during embryonic development, becoming undetectable in adulthood. Moreover, there were conspicuous maturation defects of myelinating Schwann cells; these defects were more significant in motor nerve fibers than in sensory nerve fibers.

CONCLUSIONS

Taken together, the data suggest that PMP22 is important for the normal function of neurons that express PMP22 during early development, such as cranial motor neurons and spinal sensory neurons. Moreover, PMP22 deficiency differentially affects myelination between motor and sensory nerves, which may have contributed to the unique clinical phenotype in the patient with an absence of PMP22.

Item Type: Article
Additional Information: This article is accessible to all HEFT staff and students via NHS Evidence www.evidence.nhs.uk by using their HEFT Athens login IDs
Subjects: WL Nervous system. Neurology
Divisions: Womens and Childrens > Paediatrics
Related URLs:
Depositing User: Sophie Rollason
Date Deposited: 11 Jun 2014 13:03
Last Modified: 11 Jun 2014 13:03
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/239

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