title: Mutation analysis of PMP22 in Slovak patients with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies.
abstract: Charcot-Marie-Tooth disease (CMT) and related peripheral neuropathies are the most commonly inherited neurological disorders in humans, characterized by clinical and genetic heterogeneity. The most prevalent clinical entities belonging to this group of disorders are CMT type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A and HNPP are predominantly caused by a 1.5 Mb duplication and deletion in the chromosomal region 17p11.2, respectively, and less frequently by other mutations in the peripheral myelin protein 22 (PMP22) gene. Despite being relatively common diseases, they haven't been previously studied in the Slovak population. Therefore, the aim of this study was to identify the spectrum and frequency of PMP22 mutations in the Slovak population by screening 119 families with CMT and 2 families with HNPP for causative mutations in this gene. The copy number determination of PMP22 resulted in the detection of CMT1A duplication in 40 families and the detection of HNPP deletion in 7 families, 6 of which were originally diagnosed as CMT. Consequent mutation screening of families without duplication or deletion using dHPLC and sequencing identified 6 single base changes (3 unpublished to date), from which only c.327C>A (Cys109X) present in one family was provably causative. These results confirm the leading role of PMP22 mutation analysis in the differential diagnosis of CMT and show that the spectrum and frequency of PMP22 mutations in the Slovak population is comparable to that seen in the global population.
authors: Department of Molecular Biology, Comenius University, Bratislava, Slovak Republic. resko.peter@gmail.com
authors: Peter
authors: P
authors: Resko
authors: Jan
authors: J
authors: Radvansky
authors: Zuzana
authors: Z
authors: Odnogova
authors: Marian
authors: M
authors: Baldovic
authors: Gabriel
authors: G
authors: Minarik
authors: Helena
authors: H
authors: Polakova
authors: Roland
authors: R
authors: Palffy
authors: Ludevit
authors: L
authors: Kadasi
mesh_terms: D001176:Arthrogryposis / Q000235:genetics*; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis / Q000379:methods*; D004594:Electrophysiology / Q000379:methods; D018628:Gene Dosage; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D017354:Point Mutation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D018154:Slovakia
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human