Charcot‐Marie‐Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families. (24th September 2015)

• Record Type: Journal Article
• Authors: Hyun, Young Se; Lee, Jinho; Kim, Hye Jin; Hong, Young Bin; Koo, Heasoo; Smith, Alec S.T.; Kim, Deok‐Ho; Choi, Byung‐Ok; Chung, Ki Wha
• Is Part Of: Annals of human genetics. Volume 79:Number 6(2015:Nov.)
• Page Start: 460
• Page End: 469
• Publication Date: 2015-09-24
• Subjects: Human genetics -- Periodicals; 599.935
• DOI: 10.1111/ahg.12134
• Languages: English
• ISSNs: 0003-4800

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Charcot‐Marie‐Tooth disease type 4H (CMT4H) is an autosomal recessive demyelinating subtype of peripheral enuropathies caused by mutations in the <italic>FGD4</italic> 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 <italic>FGD4</italic> as the underlying cause in both families (p.Arg468Gln and c.1512‐2A&gt;C in FC73, p.Met345Thr and c.2043+1G&gt;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 <italic>in silico</italic> 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. <italic>FGD4</italic> assay could be considered as a means of molecular diagnosis for sporadic cases of demyelinating CMT with slow progression.</p> </abstract>