We studied the peripheral myelin protein gene PMP-22 in a large Sardinian family with Charcot-Marie-Tooth disease type 1A (CMT1A), in which the duplication commonly found in CMT1A was absent, but with evidence of linkage on chromosome 17.
Recently, it has been demonstrated that the HMSN Ia phenotype results either from a duplication of chromosome 17p11.2 or from a point mutation in the peripheral nerve-specific PMP-22 gene which is located in the duplication.
Increased gene dosage or altered PMP-22 expression in the peripheral nervous system are therefore possible mechanisms by which PMP-22 is involved in CMT1A.
These observations further implicate PMP-22 as a candidate gene for CMT1A, and suggest that over-expression of this gene may be one mechanism that produces the CMT1A phenotype.
The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.