Small mutations of the DMD gene in Taiwanese families.
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.
Hwa
Hsiao-Lin
HL
Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
Chang
Yih-Yuan
YY
Huang
Chien-Hao
CH
Chen
Chung-Hsiung
CH
Kao
Yen-Shi
YS
Jong
Yuh-Jyh
YJ
Chao
Mei-Chyn
MC
Ko
Tsang-Ming
TM
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
D018389:Codon, Nonsense; C484258:DMD protein, human; D016189:Dystrophin