Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families

Young Se Hyun, Jinho Lee, Hye Jin Kim, Young Bin Hong, Heasoo Koo, Alec S.T. Smith, Deok Ho Kim, Byung Ok Choi, Ki Wha Chung

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)460-469
Number of pages10
JournalAnnals of Human Genetics
Issue number6
StatePublished - Nov 2015
Externally publishedYes


  • Charcot-Marie-Tooth disease type 4H (CMT4H)
  • Compound heterozygous mutations
  • Exome sequencing
  • FGD4
  • Korean
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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