ABSTRACT
A 1.5 Mb duplication on chromosome 17p11.2 is typical for the great majority of patients suffering from Charcot-Marie-Tooth type 1A (CMT1A) disease. A female child of 4 years with clinical signs and symptoms of a demyelinating neuropathy was examined for the presence of this duplication. Analysis of MspI polymorphisms in DNA extracted from peripheral blood failed due to homozygosity for probes pVAW409R3a and pEW401HE. Also, no EcoRI/SacI 3.2 kb junction fragment or dosage difference with probe pLR7.8, characteristic of the CMT1A duplication, was found. However, fluorescence in situ hybridization (FISH) analysis with the PMP22 specific probe c132G8 revealed in peripheral blood lymphocytes 60% of interphase nuclei with CMT1A duplication indicating the probability of mosaicism. In interphase nuclei extracted from nerve tissue the duplication was detectable in 88%, in muscle tissue in 72% of the analyzed nuclei. This suggests the presence of a somatic CMT1A duplication mosaicism that can only be reliably detected by FISH. The early onset and severity of the phenotype indicates that the hypothesized somatic reversion is probably fixed to early developmental stages.