Abstract
One third of mutations responsible for Duchenne or Becker muscular dystrophy (DMD/BMD) represent point mutations or other small sequence alterations not readily detectable by Southern blot analysis or multiplex amplification. Here, we report results of a comprehensive point mutation search that yielded seven new sequence variations and one novel polymorphism. We also summarize known mutations, polymorphisms and other small nucleotide variations in the DMD gene. To date, 12 nonsense mutations, two missense mutations, six microdeletions and one microinsertion have been reported in the coding sequence and a further six mutations in splice sites all of which were made responsible for the disease. Twelve polymorphisms with frequencies suitable for diagnostic purposes have been detected. A further 28 differences from the published sequence of the coding sequence or the promotor region are described.
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References
Abbs S, Roberts RG, Mathews CG, Bentley DR, Bobrow M (1990) Accurate assessment of intragenic recombination frequency within the Duchenne muscular dystrophy gene. Genomics 7:602–606
Baserga JS, Benz JE (1988) Nonsense mutations in the betaglobin gene affect mRNA metabolism. Proc Natl Acad Sci 85:2056–2060
Beggs AH, Koenig M, Boyce FM, Kunkel LM (1990) Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 86:45–48
Bulman DE, Gangopadhyay SB, Bebchuck KG, Worton RG, Ray PN (1991) Point mutation in the human dystrophin gene: identification through Western blot analysis. Genomics 10:457–460
Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT (1988) Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res 16:11141–11156
Chamberlain JS, Pearlman JA, Muzny DM, Civetello A, Farwell NF, Malek R, Powaser P, Reeves AA, Lee C, Caskey CT (1991) Murine dystrophin cDNA sequence. Genebank accession no M68859
Cooper DN, Krawczak (1990) The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions. Hum Genet 85:55–74
Dietz HC, Valle D, Francomano CA, Kendzior RJ Jr, Pyeritz RE, Cutting GR (1993) The skipping of constitutive exons in vivo induced by nonsense mutations. Science 25:680–683
Fisher CW, Fisher CR, Chuang JL, Lau KS, Chuang DT, Cox RP (1993) Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple-exon skipping as a secondary effect of the mutations. Am J Hum Genet 52:414–424
Grompe M (1993) The rapid detection of unknown mutations in nucleic acids. Nature Genet 5:111–117
Kiliman MW, Pizzuti A, Grompe M, Caskey CT (1992) Point mutations and polymorphisms in the human dystrophin gene identified in genomic DNA sequences amplified by multiplex PCR. Hum Genet 89:253–258
Klamut HJ, Gangopadhyay SB, Worton RG, Ray PN (1990) Molecular and functional analysis of the muscle-specific promoter region of the Duchenne muscular dystrophy gene. Mol Cell Biol 10:193–205
Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM (1987) Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50:509–517
Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53:219–228
Lemaire C, Heilig RM, Mandel JL (1988) The chicken dystrophin cDNA: striking conservation of the C-terminal coding and 3′ untranslated regions between man and chicken. EMBOJ 7:4157–4162
Lenk U, Hanke R, Thiele H, Speer A (1993) Point mutations at the carboxy terminus of the human dystrophin gene: implications for an association with mental retardation in DMD patients. Hum Mol Genet 2:1877–1881
Love DR, England SB, Speer A, Marsden RF, Bloomfield JF, Roche AL, Cross GS, Mountford RC, Smith TJ, Davies KE (1991) Sequences of junction fragments in the deletion-prone region of the dystrophin gene. Genomics 10:57–67
Matsuo M, Masumura T, Nakajima T, Yoshihiko K, Takumi HS, Nishio H, Koga J, Nakamura H (1990) A very small frameshifting deletion within exon 19 of the Duchenne muscular dystrophy gene. Biochem Biophys Res Commun 170:963–967
Matsuo M, Nishio H, Kitoh Y, Francke U, Nakamura H (1992) Partial deletion of a dystrophin gene leads to exon skipping and to loss of an intra-exon hairpin structure from the predicted mRNA precursor. Biochem Biophys Res Commun 182:495–500
Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM (1988) An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2:90–95
Muntoni F, Cau M, Congiu R, Congia M, Cao A, Melis MA (1993) Identification of a novel T-insertion polymorphism at the DMD locus. Hum Genet 92:103
Niemann-Seyde S, Slomski R, Rininsland F, Ellermeyer U, Kwiatkowska J, Reiss J (1992) Molecular genetic analysis of 67 patients with Duchenne/Becker muscular dystrophy. Hum Genet 90:65–70
Nigro V, Politano L, Nigro G, Romano SC, Colonna Romano S, Molinari AM, Puca GA (1992) Detection of a nonsense mutation in the dystrophin gene by multiple SSCP. Hum Mol Genet 1:517–520
Prior TW, Papp AC, Snyder PJ, Burghes AHM, Sedra MS, Western LM, Bartello C, Mendell JR (1993 a) Identification of two point mutations and a one base deletion in exon 19 of the dystrophin gene by heteroduplex formation. Hum Mol Genet 2:311–313
Prior TW, Papp AC, Snyder PJ, Burghes AHM, Bartolo C, Sedra MS, Western LM, Mendell JR (1993 b) A missense mutation in the dystrophin gene in a Duchenne muscular dystrophy patient. Nature Genet 4:357–360
Prior TW, Papp AC, Snyder PJ, Burghes AHM, Sedra MS, Western LM, Bartolo C, Mendell JR (1993 c) Exon 44 nonsense mutation in two Duchenne muscular dystrophy brothers detected by heteroduplex analysis. Hum Mutat 2:192–195
Prior TW, Papp AC, Snyder PJ, Sedra MS (1993 d) Detection of an exon 53 polymorphism in the dystrophin gene. Hum Genet 92:302–304
Reiss J, Lenz U, Rininsland F, Ballhausen P, Drews D, Posselt HG (1992) A novel CFTR mutation, 4035 delA, detected by nonradioactive SSCP analysis. Hum Genet 90:303–304
Rininsland F, Hahn A, Niemann-Seyde S, Slomski R, Hanefeld F, Reiss J (1992) Identification of a new DMD gene deletion by ectopic transcript analysis. J Med Genet 29:647–651
Roberts RG, Bobrow M, Bentley DR (1992) Point mutations in the dystrophin gene. Proc Natl Acad Sci USA 89:2331–2335
Roberts RG, Coffey AJ, Bobrow M, Bentley DR (1993) Exon structure of the human dystrophin gene. Genomics 16:536–538
Rosenthal A, Speer A, Billwitz H, Cross GS, Forrest SM, Davies KE (1989) Two human cDNA molecules coding for the Duchenne muscular dystrophy (DMD) locus are highly homologous. Nucleic Acids Res 17:5391
Saad FA, Vitiello L, Merlini L, Mostacciuolo ML, Oliviero S, Danieli GA (1992) A 3′ consensus splice mutation in the human dystrophin gene detected by a screening for intra-exonic deletions. Hum Mol Genet 1:345–346
Saad FA, Vita G, Mora M, Morandi L, Vitiello L, Oliviero S, Danieli GA (1993) A novel nonsense mutation in the human dystrophin gene. Hum Mutat 2:314–316
Sarkar G, Yoon H-S, Sommer SS (1992) Dideoxy fingerprinting (ddF): a rapid and efficient screen for the presence of mutations. Genomics 13:441–443
Tuffery S, Moine P, Demaille J, Claustres M (1993) Base substitutions in the human dystrophin gene: detection by using the single-strand conformation polymorphism (SSCP) technique. Hum Mutat 2:368–374
Will K, Reiss J, Dean M, Schlösser M, Slomski R, Schmidtke J, Stuhrmann M (1993) CFTR transcripts are undetectable in lymphocytes and respiratory epithelial cells of a CF patient homozygous for the nonsense mutation R553X. J Med Genet 30:833–837
Winnard AV, Jia-Hsu Y, Gibbs RA, Mendell JR, Burghes AHM (1992) Identification of a 2 base-pair nonsense mutation causing a cryptic splice site in a DMD patient. Hum Mol Genet 1:645–646
Yau SC, Roberts RG, Bentley DR, Mathew CG, Bobrow M (1991) A MseI polymorphism in exon 48 of the dystrophin gene. Nucleic Acids Res 19:5803
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Rininsland, F., Reiss, J. Microlesions and polymorphisms in the Duchenne/Becker muscular dystrophy gene. Hum Genet 94, 111–116 (1994). https://doi.org/10.1007/BF00202854
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DOI: https://doi.org/10.1007/BF00202854