title: Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families.
abstract: Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive demyelinating subtype of peripheral enuropathies caused by mutations in the FGD4 gene. Most CMT4H patients are in consanguineous Mediterranean families characterized by early onset and slow progression. We identified two CMT4H patients from a Korean CMT cohort, and performed a detailed genetic and clinical analysis in both cases. Both patients from nonconsanguineous families showed characteristic clinical manifestations of CMT4H including early onset, scoliosis, areflexia, and slow disease progression. Exome sequencing revealed novel compound heterozygous mutations in FGD4 as the underlying cause in both families (p.Arg468Gln and c.1512-2A>C in FC73, p.Met345Thr and c.2043+1G>A (p.Trp663Trpfs*30) in FC646). The missense mutations were located in highly conserved RhoGEF and PH domains which were predicted to be pathogenic in nature by in silico modeling. The CMT4H occurrence frequency was calculated to 0.7% in the Korean demyelinating CMT patients. This study is the first report of CMT4H in Korea. FGD4 assay could be considered as a means of molecular diagnosis for sporadic cases of demyelinating CMT with slow progression.
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju, Korea.
authors.forename: Young Se
authors.initials: YS
authors.lastname: Hyun
authors.affiliation: Department of Neurology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jinho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Heasoo
authors.initials: H
authors.lastname: Koo
authors.affiliation: Department of Bioengineering, University of Washington, WA, USA.
authors.forename: Alec S T
authors.initials: AS
authors.lastname: Smith
authors.affiliation: Department of Bioengineering, University of Washington, WA, USA.
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Sungkyunkwan University School of Medicine, Seoul, Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju, Korea.
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D056910:Republic of Korea; D055815:Young Adult
chemical_list: C485164:FGD4 protein, human; D008840:Microfilament Proteins
keywords: Charcot-Marie-Tooth disease type 4H (CMT4H); FGD4; Korean; compound heterozygous mutations; exome sequencing; peripheral neuropathy