Impaired Intracellular Trafficking Is a Common Disease Mechanism ofPMP22Point Mutations in Peripheral Neuropathies
The most common forms of hereditary motor and sensory neuropathies (HMSN) or Charcot–Marie–Tooth disease (CMT) are associated with mutations affecting myelin genes in the peripheral nervous system. A minor subgroup of CMT type 1A (CMT1A) is caused by point mutations in the gene encoding the peripher...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
1999-02-01
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| Series: | Neurobiology of Disease |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996198902273 |
| Summary: | The most common forms of hereditary motor and sensory neuropathies (HMSN) or Charcot–Marie–Tooth disease (CMT) are associated with mutations affecting myelin genes in the peripheral nervous system. A minor subgroup of CMT type 1A (CMT1A) is caused by point mutations in the gene encoding the peripheral myelin protein 22 (PMP22). To study the mechanisms by which these mutations cause the CMT pathology, we transiently transfected COS7 and Schwann cells with wild-type and PMP22 expression constructs carrying six representative dominant orde novopoint mutations and one putative recessive point mutation. All but one of the first group of mutant PMP22 proteins failed to be incorporated into the plasma membrane and were retained in intracellular compartments of transfected cells. Surprisingly, the recessive PMP22 mutation produced a protein that was also mildly impaired in trafficking. Thus, our results suggest a common disease mechanism underlying the pathology of CMT1A due to PMP22 point mutations. |
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| ISSN: | 1095-953X |