title: MPZ mutation in an early-onset Charcot-Marie-Tooth disease type 1B family by genome-wide linkage analysis.
abstract: Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous peripheral neuropathy. The objective of this study was to find the causative mutation(s) in a demyelinating autosomal dominant CMT family. A high density SNP-based genome-wide linkage scan was performed, and causative mutations were determined by sequencing of candidate genes in the linkage disequilibrium region. Linkage analysis mapped the underlying gene to a region on chromosome 1q22-q23 with a maximum two-point LOD score of 2.036. Sequencing analysis revealed a novel c.243C>G (His81Gln) mutation in the MPZ gene, which encodes the major integral membrane protein of the peripheral nerve system. MPZ is well known as a CMT-causative gene with wide phenotypic spectrum. The clinical symptoms were more similar to those of patients with the His81Arg than patients with the His81Tyr mutation. The novel mutation completely co-segregated with affected members, and was not found in controls. Therefore, we suggest that the identified mutation in MPZ is the underlying cause of CMT in the family. In addition, this study demonstrated that the clinical phenotypes may be variable with different mutations at the same site in the MPZ gene.
authors.affiliation: Department of Neurology, Ewha Womans University School of Medicine, Yangcheon-ku, Seoul 158-710, Republic of Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Kim
authors.forename: Sumera
authors.initials: S
authors.lastname: Kanwal
authors.forename: Young Se
authors.initials: YS
authors.lastname: Hyun
authors.forename: Sun Wha
authors.initials: SW
authors.lastname: Park
authors.forename: Heasoo
authors.initials: H
authors.lastname: Koo
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Yoo
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Hyun
authors.forename: Kee Duk
authors.initials: KD
authors.lastname: Park
authors.forename: Kyoung-Gyu
authors.initials: KG
authors.lastname: Choi
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People; D016022:Case-Control Studies; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D055724:Electrophysiological Phenomena; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D018993:Myelin P0 Protein / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: C560547:MPZ protein, human; D018993:Myelin P0 Protein