title: X-linked Charcot-Marie-Tooth disease type 6 (CMTX6) patients with a p.R158H mutation in the pyruvate dehydrogenase kinase isoenzyme 3 gene.
abstract: Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene have been found to cause X-linked dominant CMT type 6 (CMTX6). This study identified the p.R158H PDK3 mutation after screening 67 probable X-linked CMT families. The mutation fully segregated with the phenotype, and genotyping the family indicated the mutation arose on a different haplotype compared with the original Australian CMTX6 family. Results of bisulphite sequencing suggest that methylated deamination of a CpG dinucleotide may cause the recurrent p.R158H mutation. The frequency of the p.R158H PDK3 mutation in Koreans is very rare. Magnetic resonance imaging revealed fatty infiltration involving distal muscles in the lower extremities. In addition, fatty infiltrations were predominantly observed in the soleus muscles, with a lesser extent in tibialis anterior muscles. This differs from demyelinating CMT1A patients and is similar to axonal CMT2A patients. The clinical, neuroimaging, and electrophysiological findings from a second CMTX6 family with the p.R158H PDK3 mutation were similar to the axonal neuropathy reported in the Australian family.
authors.affiliation: Northcott Neuroscience Laboratory, ANZAC Research Institute & Sydney Medical School University of Sydney, Sydney, Australia.|Molecular Medicine Laboratory, Concord Hospital, Sydney, Australia.
authors.forename: Marina L
authors.initials: ML
authors.lastname: Kennerson
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Korea.
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Northcott Neuroscience Laboratory, ANZAC Research Institute & Sydney Medical School University of Sydney, Sydney, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Siddell
authors.affiliation: Northcott Neuroscience Laboratory, ANZAC Research Institute & Sydney Medical School University of Sydney, Sydney, Australia.
authors.forename: Aditi
authors.initials: A
authors.lastname: Kidambi
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju, Korea.
authors.forename: Sung M
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Neuroscience Center, Samsung Medical Center, Seoul, Korea.|Stem Cell & Regenerative Medicine Center, Kongju National University, Gongju, Korea.
authors.forename: Young B
authors.initials: YB
authors.lastname: Hong
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun H
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju, Korea.
authors.forename: Ki W
authors.initials: KW
authors.lastname: Chung
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Korea.|Stem Cell & Regenerative Medicine Center, Kongju National University, Gongju, Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
chemical_list: C000631431:PDK3 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases
keywords: CMTX6; bisulphite sequencing; neuropathy; pyruvate dehydrogenase kinase isoenzyme 3 (PDK3); whole-exome sequencing (WES)