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MIM.118220 17p11.2

Sunday 5 February 2006

In CMT1A, there is a duplication of a large region of chromosome 17p11.2-p12, resulting in "segmental trisomy" of the duplicated region.

The duplicated segment includes the gene for peripheral myelin protein 22 (PMP22), but whether the disease is caused by overexpression of PMP22, by gene dosage effect, or by duplication of other adjacent genes is not clear.

A separate genetic locus on chromosome 1 involves myelin protein zero (MPZ) but produces an identical clinical phenotype (HMSN IB).

A third set of pedigrees shows linkage to chromosome 16p, and is associated with mutations in a gene whose product is involved in protein degradation pathways.

CMT1 is a demyelinating neuropathy, both by nerve conduction velocity studies and pathologically. Histologic examination shows the consequences of repetitive demyelination and remyelination, with multiple onion bulbs, more pronounced in distal nerves than in proximal nerves).

The axon is often present in the center of the onion bulb, and the myelin sheath is usually thin or absent. The redundant layers of Schwann cell hyperplasia surrounding individual axons are associated with enlargement of individual peripheral nerves that may be individually palpable, which has led to the term hypertrophic neuropathy.

In the longitudinal plane, individual segments of the axon may show evidence of segmental demyelination. Autopsy studies of affected individuals have shown degeneration of the posterior columns of the spinal cord.