title: Molecular analysis in Japanese patients with Charcot-Marie-Tooth disease: DGGE analysis for PMP22, MPZ, and Cx32/GJB1 mutations.
abstract: Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder and is traditionally classified into two major types, CMT type 1 (CMT1) and CMT type 2 (CMT2). Most CMT1 patients are associated with the duplication of 17p11.2-p12 (CMT1A duplication) and small numbers of patients have mutations of the peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), connexin 32 (Cx32/GJB1), and early growth response 2 (EGR2) genes. Some mutations of MPZ and Cx32 were also associated with the clinical CMT2 phenotype. We constructed denaturing gradient gel electrophoresis (DGGE) analysis as a screening method for PMP22, MPZ, and Cx32 mutations and studied 161 CMT patients without CMT1A duplication. We detected 27 mutations of three genes including 15 novel mutations; six of PMP22, three of MPZ, and six of Cx32. We finally identified 21 causative mutations in 22 unrelated patients and five polymorphic mutations. Eighteen of 22 patients carrying PMP22, MPZ, or Cx32 mutations presented with CMT1 and four of them with MPZ or Cx32 mutations presented with the CMT2 phenotype. DGGE analysis was sensitive for screening for those gene mutations, but causative gene mutation was not identified in many of the Japanese patients with CMT, especially with CMT1. Other candidate genes should be studied to elucidate the genetic basis of Japanese CMT patients.
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Chikahiko
authors.initials: C
authors.lastname: Numakura
authors.forename: Changqing
authors.initials: C
authors.lastname: Lin
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikegami
authors.forename: Per
authors.initials: P
authors.lastname: Guldberg
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods*; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D009154:Mutation; D018993:Myelin P0 Protein / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics; D009691:Nucleic Acid Denaturation; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D000097002:Gap Junction beta-1 Protein; C073687:PMP22 protein, human