Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Jan;83(1):95–99. doi: 10.1172/JCI113890

Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia.

E R McCabe 1, J Towbin 1, J Chamberlain 1, L Baumbach 1, J Witkowski 1, G J van Ommen 1, M Koenig 1, L M Kunkel 1, W K Seltzer 1
PMCID: PMC303648  PMID: 2536049

Abstract

Genomic DNA from a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia was investigated using cDNA probes for the Duchenne muscular dystrophy (DMD) locus. Genomic probes had not detected a deletion in this patient. Southern analysis of Hind III-digested genomic DNA from this patient identified a deletion when the three distal Hinc II DMD cDNA fragments were used as probes. The deletion began in the genomic region corresponding to the 1.05-kb Hinc II cDNA fragment and extended through the 3' end of the DMD gene. This represents a centromeric breakpoint that corresponds to a position approximately 10.2-10.6 kb from the 5' end of the 14-kb DMD cDNA. These investigations demonstrate the value of the DMD cDNA probes for improved diagnoses in patients with molecular lesions involving the DMD locus. Furthermore, this novel deletion involving the coding portion of the 3' end of the DMD gene assists in the ordering of exons in this region and will provide insight into the functional role of the carboxy terminus of the DMD gene product, dystrophin.

Full text

PDF
96

Images in this article

96Image
on p.96
96Image
on p.96
96Image
on p.96
96Image
on p.96
97Image
on p.97
97Image
on p.97

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brunk C. F., Jones K. C., James T. W. Assay for nanogram quantities of DNA in cellular homogenates. Anal Biochem. 1979 Jan 15;92(2):497–500. doi: 10.1016/0003-2697(79)90690-0. [DOI] [PubMed] [Google Scholar]
  2. Chamberlain J. S., Pearlman J. A., Muzny D. M., Gibbs R. A., Ranier J. E., Caskey C. T., Reeves A. A. Expression of the murine Duchenne muscular dystrophy gene in muscle and brain. Science. 1988 Mar 18;239(4846):1416–1418. doi: 10.1126/science.3347839. [DOI] [PubMed] [Google Scholar]
  3. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davison M. D., Critchley D. R. alpha-Actinins and the DMD protein contain spectrin-like repeats. Cell. 1988 Jan 29;52(2):159–160. doi: 10.1016/0092-8674(88)90503-x. [DOI] [PubMed] [Google Scholar]
  5. Dunger D. B., Davies K. E., Pembrey M., Lake B., Pearson P., Williams D., Whitfield A., Dillon M. J. Deletion on the X chromosome detected by direct DNA analysis in one of two unrelated boys with glycerol kinase deficiency, adrenal hypoplasia, and Duchenne muscular dystrophy. Lancet. 1986 Mar 15;1(8481):585–587. doi: 10.1016/s0140-6736(86)92811-4. [DOI] [PubMed] [Google Scholar]
  6. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  7. Francke U., Harper J. F., Darras B. T., Cowan J. M., McCabe E. R., Kohlschütter A., Seltzer W. K., Saito F., Goto J., Harpey J. P. Congenital adrenal hypoplasia, myopathy, and glycerol kinase deficiency: molecular genetic evidence for deletions. Am J Hum Genet. 1987 Mar;40(3):212–227. [PMC free article] [PubMed] [Google Scholar]
  8. Guggenheim M. A., McCabe E. R., Roig M., Goodman S. I., Lum G. M., Bullen W. W., Ringel S. P. Glycerol kinase deficiency with neuromuscular, skeletal, and adrenal abnormalities. Ann Neurol. 1980 May;7(5):441–449. doi: 10.1002/ana.410070509. [DOI] [PubMed] [Google Scholar]
  9. Hammond J., Howard N. J., Brookwell R., Purvis-Smith S., Wilcken B., Hoogenraad N. Proposed assignment of loci for X-linked adrenal hypoplasia and glycerol kinase genes. Lancet. 1985 Jan 5;1(8419):54–54. doi: 10.1016/s0140-6736(85)91009-8. [DOI] [PubMed] [Google Scholar]
  10. Hart K. A., Hodgson S., Walker A., Cole C. G., Johnson L., Dubowitz V., Bobrow M. DNA deletions in mild and severe Becker muscular dystrophy. Hum Genet. 1987 Mar;75(3):281–285. doi: 10.1007/BF00281075. [DOI] [PubMed] [Google Scholar]
  11. Hejtmancik J. F., Harris S. G., Tsao C. C., Ward P. A., Caskey C. T. Carrier diagnosis of Duchenne muscular dystrophy using restriction fragment length polymorphisms. Neurology. 1986 Dec;36(12):1553–1562. doi: 10.1212/wnl.36.12.1553. [DOI] [PubMed] [Google Scholar]
  12. Hoffman E. P., Brown R. H., Jr, Kunkel L. M. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987 Dec 24;51(6):919–928. doi: 10.1016/0092-8674(87)90579-4. [DOI] [PubMed] [Google Scholar]
  13. Kan Y. W., Dozy A. M., Trecartin R., Todd D. Identification of a nondeletion defect in alpha-thalassemia. N Engl J Med. 1977 Nov 17;297(20):1081–1084. doi: 10.1056/NEJM197711172972002. [DOI] [PubMed] [Google Scholar]
  14. Koenig M., Hoffman E. P., Bertelson C. J., Monaco A. P., Feener C., Kunkel L. M. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987 Jul 31;50(3):509–517. doi: 10.1016/0092-8674(87)90504-6. [DOI] [PubMed] [Google Scholar]
  15. Kunkel L. M., Hejtmancik J. F., Caskey C. T., Speer A., Monaco A. P., Middlesworth W., Colletti C. A., Bertelson C., Müller U., Bresnan M. Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature. 1986 Jul 3;322(6074):73–77. doi: 10.1038/322073a0. [DOI] [PubMed] [Google Scholar]
  16. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Labarca C., Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980 Mar 1;102(2):344–352. doi: 10.1016/0003-2697(80)90165-7. [DOI] [PubMed] [Google Scholar]
  18. McCabe E. R., Fennessey P. V., Guggenheim M. A., Miles B. S., Bullen W. W., Sceats D. J., Goodman S. I. Human glycerol kinase deficiency with hyperglycerolemia and glyceroluria. Biochem Biophys Res Commun. 1977 Oct 24;78(4):1327–1333. doi: 10.1016/0006-291x(77)91437-1. [DOI] [PubMed] [Google Scholar]
  19. Old J. M., Briand P. L., Purvis-Smith S., Howard N. J., Wilcken B., Hammond J., Pearson P., Cathelineau L., Williamson R., Davies K. E. Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis. Lancet. 1985 Jan 12;1(8420):73–75. doi: 10.1016/s0140-6736(85)91966-x. [DOI] [PubMed] [Google Scholar]
  20. Poncz M., Solowiejczyk D., Harpel B., Mory Y., Schwartz E., Surrey S. Construction of human gene libraries from small amounts of peripheral blood: analysis of beta-like globin genes. Hemoglobin. 1982;6(1):27–36. doi: 10.3109/03630268208996930. [DOI] [PubMed] [Google Scholar]
  21. Seltzer W. K., Firminger H., Klein J., Pike A., Fennessey P., McCabe E. R. Adrenal dysfunction in glycerol kinase deficiency. Biochem Med. 1985 Apr;33(2):189–199. doi: 10.1016/0006-2944(85)90027-4. [DOI] [PubMed] [Google Scholar]
  22. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  23. Wapenaar M. C., Kievits T., Hart K. A., Abbs S., Blonden L. A., den Dunnen J. T., Grootscholten P. M., Bakker E., Verellen-Dumoulin C., Bobrow M. A deletion hot spot in the Duchenne muscular dystrophy gene. Genomics. 1988 Feb;2(2):101–108. doi: 10.1016/0888-7543(88)90090-0. [DOI] [PubMed] [Google Scholar]
  24. Wieringa B., Hustinx T., Scheres J., Renier W., ter Haar B. Complex glycerol kinase deficiency syndrome explained as X-chromosomal deletion. Clin Genet. 1985 May;27(5):522–523. doi: 10.1111/j.1399-0004.1985.tb00244.x. [DOI] [PubMed] [Google Scholar]
  25. van Ommen G. J., Verkerk J. M., Hofker M. H., Monaco A. P., Kunkel L. M., Ray P., Worton R., Wieringa B., Bakker E., Pearson P. L. A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X-chromosome. Cell. 1986 Nov 21;47(4):499–504. doi: 10.1016/0092-8674(86)90614-8. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES