title: Founder mutation causes classical Fukuyama congenital muscular dystrophy (FCMD) in Chinese patients.
abstract: OBJECTIVE
  Fukuyama congenital muscular dystrophy (FCMD) is a congenital muscular dystrophy rarely reported outside Japan. Here, we report three patients with Fukuyama congenital muscular dystrophy (FCMD) in China who shared a similar clinical phenotype and 3-kb insertion in the FKTN 3' untranslated region.
  
  
  METHODS
  Immunofluorescence staining was undertaken on muscle biopsies from three patients using alpha dystroglycan antibody (IIH6). Genomic DNA from patients and parents was extracted from peripheral blood leukocytes. Polymerase chain reaction and DNA sequencing were employed to analyze the exons and surrounding intron sequences of the fukutin (FKTN) gene to detect mutations. Haplotype analysis was also performed on each patient and their parents.
  
  
  RESULTS
  All patients had delayed mental and motor development, febrile convulsions, muscle weakness, and moderate to significant raised levels of serum creatine kinase (7000-11,160 U/L, 25-60×normal). Brain MRI scans showed micropolygyria and extensive dysplasia in the white matter and brainstem. Electromyography revealed myopathic changes. Muscle immunofluorescence studies demonstrated reduced IIH6 staining. Genetic testing showed compound heterozygous mutations of FKTN. Cases 1 and 2 had a c.139C>T (p.Arg47(∗)) heterozygous mutation. Case 3 had a c.346C>T (p.Gln116(∗)) heterozygous mutation.
  
  
  CONCLUSIONS
  All patients had a heterozygous 3-kb insertion in the FKTN 3' untranslated region. Haplotype analyses suggested that these patients had the same haplotype as Japanese patients.
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Haipo
authors: H
authors: Yang
authors: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors: Kazuhiro
authors: K
authors: Kobayashi
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Shuo
authors: S
authors: Wang
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Hui
authors: H
authors: Jiao
authors: Department of Radiology, Peking University First Hospital, Beijing 100034, China.
authors: Jiangxi
authors: J
authors: Xiao
authors: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors: Tatsushi
authors: T
authors: Toda
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors: Xiru
authors: X
authors: Wu
authors: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Electronic address: xh_bjbj@163.com.
authors: Hui
authors: H
authors: Xiong
mesh_terms: D020413:3' Untranslated Regions; D044466:Asian People; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D018703:Founder Effect; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D058494:Walker-Warburg Syndrome / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C113587:FKTN protein, human; D008565:Membrane Proteins
keywords: 3-kb insertion; FKTN; Founder mutation; Fukuyama congenital muscular dystrophy; Haplotype analysis