title: Small mutations of the DMD gene in Taiwanese families.
abstract: OBJECTIVE
  Duchenne/Becker muscular dystrophies are X-linked recessive disorders caused by mutations in the Duchenne muscular dystrophy (DMD) gene. We aimed to demonstrate the small mutation patterns of the DMD gene in Taiwanese subjects.
  
  
  METHODS
  We sequenced all 79 exons of the DMD gene in 33 unrelated Taiwanese families in which large-scale deletions and duplications had been excluded by multiplex ligation-dependent probe amplification.
  
  
  RESULTS
  Direct sequencing detected 23 different mutations from 26 families, including 15 novel mutations and eight previously reported ones. The 15 novel mutations consisted of seven substitutions (c.1238C>G [p.S413X], c.2971G>T [p.E991X], c.3172C>T [p.Q1058X], c.7402G>T [p.E2468X], c.8022C>G [p.S2605X], c.10018T>C [p.C3340R], c.10546G>T [p.E3516X]), six small deletions (c.2202delG [p.A668fsX676], c.2268delC [p.F756fsX759], c.4611delT [p.N1537fsX1545], c.4856_4857delAA [p.K1619fsX1621], c.6638delT [p.L2213fsX2220], c.9457delT [p.C3153fsX3154]), and two small insertions (c.4351insA [p.L1451fsX1468], c.10493_10495insAAT [p.L3498X]). Twenty-two of the 23 pathologic changes disrupted the translational reading frame (13 nonsense, 7 frameshift, 2 splice-site change), whereas only one was a missense variant with known pathogenic nature. Two previously reported mutations, c.8038C>T [p.R2680X] and c.10108C>T [p.R3370X] were detected in two and three unrelated families, respectively.
  
  
  CONCLUSIONS
  Most identified mutations either led to a predictable premature stop codon or resulted in splicing defects, which caused defective function of dystrophin. Our findings extend the mutation spectrum of the DMD gene. Molecular characterization of the affected families is important for genetic counseling and prenatal diagnosis.
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsiao-Lin
authors.initials: HL
authors.lastname: Hwa
authors.forename: Yih-Yuan
authors.initials: YY
authors.lastname: Chang
authors.forename: Chien-Hao
authors.initials: CH
authors.lastname: Huang
authors.forename: Chung-Hsiung
authors.initials: CH
authors.lastname: Chen
authors.forename: Yen-Shi
authors.initials: YS
authors.lastname: Kao
authors.forename: Yuh-Jyh
authors.initials: YJ
authors.lastname: Jong
authors.forename: Mei-Chyn
authors.initials: MC
authors.lastname: Chao
authors.forename: Tsang-Ming
authors.initials: TM
authors.lastname: Ko
mesh_terms: D018389:Codon, Nonsense; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D009154:Mutation; D013624:Taiwan
chemical_list: D018389:Codon, Nonsense; C484258:DMD protein, human; D016189:Dystrophin