TY - JOUR AB - 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. AD - Department of Neurology, Ewha Womans University School of Medicine, Yangcheon-ku, Seoul 158-710, Republic of Korea null Department of Biological Science and Research Center for Biotechnology, Kongju National University, 182 Sinkwan-dong, Gongju, Chungnam 314-701, Republic of Korea AU - Choi,Byung-Ok AU - Kim,Sang-Beom AU - Kanwal,Sumera AU - Hyun,Young ,Se AU - Park,Sun ,Wha AU - Koo,Heasoo AU - Yoo,Jeong ,Hyun AU - Hyun,Jae ,Won AU - Park,Kee ,Duk AU - Choi,Kyoung-Gyu AU - Chung,Ki ,Wha DA - 2011/09/01 DO - 10.3892/ijmm.2011.678 EP - 396 IS - 3 JO - Int J Mol Med KW - Charcot-Marie-Tooth disease genome-wide scan linkage analysis MPZ Korean PY - 2011 SN - 1107-3756 1791-244X SP - 389 ST - MPZ mutation in an early-onset Charcot-Marie-Tooth disease type 1B family by genome-wide linkage analysis T2 - International Journal of Molecular Medicine TI - MPZ mutation in an early-onset Charcot-Marie-Tooth disease type 1B family by genome-wide linkage analysis UR - https://doi.org/10.3892/ijmm.2011.678 VL - 28 ER -