title: Molecular diagnosis of X-linked adrenoleukodystrophy: experience from a clinical genetic laboratory in mainland China with report of 13 novel mutations.
abstract: BACKGROUND
  X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by progressive demyelination of the nervous system, adrenocortical insufficiency and increase of very long chain fatty acids (VLCFAs) in the plasma and tissues.
  
  
  METHODS
  A total of 131 individuals from 30 Chinese pedigrees were involved in this study, including 42 symptomatic patients, 44 female carriers, and 15 high-risk fetuses from 13 families. The mutation was first pinpointed through long distance RT-PCR-based RNA approach and confirmed through peripheral blood DNA approach.
  
  
  RESULTS
  A total of 28 mutations were identified, of which 19 were missense, 3 nonsense and 6 frame-shift mutations. Thirteen mutations were novel, i.e. p.R280L, p.P580L, p.G343V, p.S108X, p.R259W, p.P534R, p.fs A246, p.L576P, p.K602X, p.A314P, p.N148D, p.H283R, and p.fs R89. Two mutations occurred de novo, for they were not found in somatic cells of their parents. Three females from the same family developed AMN-like symptoms and they were heterozygous for the p.H283R mutation. Four asymptomatic boys were diagnosed as X-ALD patients and prenatal molecular diagnosis were provided for 13 X-ALD-stricken families.
  
  
  CONCLUSIONS
  Our work extended the spectrum of mutations in X-ALD and benefited genetic counseling through reliable identification of heterozygous females and asymptomatic males.
authors.affiliation: Research Center for Molecular Diagnosis of Genetic Diseases, Department of Neurology, Fuzhou General Hospital, Fuzhou City, PR China. fhlan@mail.fjmu.edu.cn
authors.forename: Fenghua
authors.initials: F
authors.lastname: Lan
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.forename: Haihua
authors.initials: H
authors.lastname: Xie
authors.forename: Lianghu
authors.initials: L
authors.lastname: Huang
authors.forename: Longfeng
authors.initials: L
authors.lastname: Ke
authors.forename: Bosheng
authors.initials: B
authors.lastname: Yang
authors.forename: Zhongyong
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics; D000326:Adrenoleukodystrophy / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007753:Laboratories; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters