Novel peripheral myelin protein 22 (PMP22) micromutations associated with variable phenotypes in Greek patients with Charcot-Marie-Tooth disease

ARTICLESir, We read with interest the paper by Taioli et al . (2011) reporting eight different micromutations of PMP22 in patients with inherited demyelinating neuropathies. Small frameshift insertions/deletions (indels), nonsense nucleotide substitutions and splice-site mutations led to phenotypically and pathologically variable neuropathies. Patients with mutations causing a premature or delayed stop codon had a phenotype within the hereditary neuropathy with liability to pressure palsies (HNPP) spectrum. One patient with a splice-site mutation causing an in-frame skipping of exon 4 had a CMT1 phenotype. As the authors state, micromutations of PMP22 are considered very rare causes of Charcot–Marie–Tooth (CMT) in most populations and this certainly includes our experience of PMP22 analysis in cases with CMT from the UK. We presently report three novel PMP22 micromutations identified in a Greek cohort of patients with CMT that were associated with variable clinical phenotypes, ranging from severe CMT1 of the Dejerine–Sottas disease spectrum to HNPP. These novel cases, taken together with the findings of Taioli et al . (2011) illustrate that, despite some exceptions, in-frame indels in PMP22 usually lead to CMT1 of varying severity, whereas frameshift changes more often cause HNPP.DNA was extracted from peripheral blood following standard procedures. Patients were previously found negative for the common duplication/deletion in chromosome 17 and for mutations in GJB1 and MPZ . The four coding exons (exons 2–5) of PMP22 with adjacent intronic sequences were amplified by polymerase chain reaction and sequenced on an Applied Biosystems 3730XL genetic analyser. Fragment analysis was performed with GeneMapper® software after running fragments on the 3730XL with a LIZ500 standard. RNA was obtained from peripheral blood using the Qiagen/PreAnalytix™ blood RNA system. Complementary DNA was synthesized using the Applied Biosystems high capacity complementary DNA reverse transcription kit. A 391 bp fragment of complementary DNA spanning the regions of interest …