title: Mutational analysis of Greek patients with suspected hereditary neuropathy with liability to pressure palsies (HNPP): a 15-year experience.
abstract: There has been limited information from population studies regarding the overall frequency of the common 1.5-Mb 17p11.2 deletion and even scarcer data regarding the overall frequency of PMP22 micromutations in patients with a clinical suspicion of hereditary neuropathy with liability to pressure palsies (HNPP). We have analysed 100 consecutive Greek patients referred for HNPP genetic testing over a 15-year period to our Neurogenetics Unit in Athens, a reference centre for all regions of Greece. All patients were screened for the 1.5-Mb deletion and a selected subgroup of deletion-negative patients for PMP22 micromutations. Mutation-positive and mutation-negative patients were compared for various clinical parameters. In total, 54 mutation-positive patients were identified. In index cases, the deletion frequency was 47.8%, and the PMP22 micromutation frequency was 2.2%. Within mutation-positive patients, the common deletion represented 95.7% and PMP22 micromutations 4.3% of cases. Two previously reported PMP22 micromutations (c.364_365delCC and c.79-2A>G) were detected. HNPP index cases had a 2.8-1 male-to-female ratio, similar to mutation-negative patients. A typical phenotype (recurrent or isolated palsies) was present in 82.4% of symptomatic HNPP cases, significantly higher than mutation-negative patients. Sensitivity of proposed electrophysiological diagnostic criteria for HNPP was calculated at 95.7% and specificity at 80.5%. In conclusion, the common HNPP deletion accounts for ∼50% and PMP22 micromutations for ∼2% of cases in a large consecutive cohort of patients with suspected HNPP. The mutational and phenotypic spectrum of HNPP is similar in the Greek population compared with other populations. Proposed electrophysiological diagnostic criteria perform satisfactorily in everyday clinical practice.
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Karadima
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Koutsis
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Raftopoulou
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Karolina-Maria
authors.initials: KM
authors.lastname: Karletidi
authors.affiliation: EMG Laboratory, 1st Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zambelis
authors.affiliation: EMG Laboratory, 1st Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Karandreas
authors.affiliation: Neurogenetics Unit, 1st Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Panas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001176:Arthrogryposis / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006115:Greece; D015417:Hereditary Sensory and Motor Neuropathy / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D010641:Phenotype; D058496:Smith-Magenis Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human
keywords: Greece; HNPP; PMP22 mutation; chromosome 17p11.2 deletion; hereditary neuropathy with liability to pressure palsies; population study