Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1996 Apr;33(4):284–288. doi: 10.1136/jmg.33.4.284

The molecular defect underlying canine fucosidosis.

B J Skelly 1, D R Sargan 1, M E Herrtage 1, B G Winchester 1
PMCID: PMC1050576  PMID: 8730282

Abstract

Fucosidosis is a lysosomal storage disease which affects humans and English springer spaniel dogs. The disease is recessively inherited in both species and results from a deficiency of the enzyme alpha-L-fucosidase. We have recently cloned and sequenced the canine fucosidase gene (EMBL sequence admission number X92448 (cDNA) and X92671-X92678 (individual exonic data)). The gene spans 12 kb and consists of eight exons. SSCP based mutation analysis of affected animals was carried out on the coding region of this gene both with exonic primers, and intronic primer pairs for each exon. A 14 base pair deletion of the cDNA was identified at the 3' end of exon 1 in fucosidosis affected animals. Surprisingly, PCR based genomic cloning of DNA from these animals showed an identical deletion in this DNA, ending at the start of intron 1. This change causes a frameshift and, in consequence, 25 novel codons are transcribed in exon 2 before the first of two adjacent premature stop codons is encountered.

Full text

PDF
287

Images in this article

285Image
on p.285
286Image
on p.286
287Image
on p.287

Selected References

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

  1. Abraham D., Blakemore W. F., Dell A., Herrtage M. E., Jones J., Littlewood J. T., Oates J., Palmer A. C., Sidebotham R., Winchester B. The enzymic defect and storage products in canine fucosidosis. Biochem J. 1984 Aug 15;222(1):25–33. doi: 10.1042/bj2220025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barker C., Dell A., Rogers M., Alhadeff J. A., Winchester B. Canine alpha-L-fucosidase in relation to the enzymic defect and storage products in canine fucosidosis. Biochem J. 1988 Sep 15;254(3):861–868. doi: 10.1042/bj2540861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Durand P., Borrone C., Della Cella G. Fucosidosis. J Pediatr. 1969 Oct;75(4):665–674. doi: 10.1016/s0022-3476(69)80464-6. [DOI] [PubMed] [Google Scholar]
  4. Ferrara M. L., Taylor R. M., Stewart G. J. Age at marrow transplantation is critical for successful treatment of canine fucosidosis. Transplant Proc. 1992 Oct;24(5):2282–2283. [PubMed] [Google Scholar]
  5. Hartley W. J., Canfield P. J., Donnelly T. M. A suspected new canine storage disease. Acta Neuropathol. 1982;56(3):225–232. doi: 10.1007/BF00690639. [DOI] [PubMed] [Google Scholar]
  6. Jeanpierre M. A rapid method for the purification of DNA from blood. Nucleic Acids Res. 1987 Nov 25;15(22):9611–9611. doi: 10.1093/nar/15.22.9611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kretz K. A., Cripe D., Carson G. S., Fukushima H., O'Brien J. S. Structure and sequence of the human alpha-L-fucosidase gene and pseudogene. Genomics. 1992 Feb;12(2):276–280. doi: 10.1016/0888-7543(92)90374-2. [DOI] [PubMed] [Google Scholar]
  8. Kretz K. A., Darby J. K., Willems P. J., O'Brien J. S. Characterization of EcoRI mutation in fucosidosis patients: a stop codon in the open reading frame. J Mol Neurosci. 1989;1(3):177–180. doi: 10.1007/BF02918904. [DOI] [PubMed] [Google Scholar]
  9. Littlewood J. D., Herrtage M. E., Palmer A. C. Neuronal storage disease in English springer spaniels. Vet Rec. 1983 Jan 22;112(4):86–87. doi: 10.1136/vr.112.4.86. [DOI] [PubMed] [Google Scholar]
  10. Myers T. W., Gelfand D. H. Reverse transcription and DNA amplification by a Thermus thermophilus DNA polymerase. Biochemistry. 1991 Aug 6;30(31):7661–7666. doi: 10.1021/bi00245a001. [DOI] [PubMed] [Google Scholar]
  11. Occhiodoro T., Beckmann K. R., Morris C. P., Hopwood J. J. Human alpha-L-fucosidase: complete coding sequence from cDNA clones. Biochem Biophys Res Commun. 1989 Oct 16;164(1):439–445. doi: 10.1016/0006-291x(89)91739-7. [DOI] [PubMed] [Google Scholar]
  12. Occhiodoro T., Hopwood J. J., Morris C. P., Anson D. S. Correction of alpha-L-fucosidase deficiency in fucosidosis fibroblasts by retroviral vector-mediated gene transfer. Hum Gene Ther. 1992 Aug;3(4):365–369. doi: 10.1089/hum.1992.3.4-365. [DOI] [PubMed] [Google Scholar]
  13. Orita M., Iwahana H., Kanazawa H., Hayashi K., Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766–2770. doi: 10.1073/pnas.86.8.2766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  15. Seo H. C., Heidemann P. H., Lutz E., O'Brien J. S. A nonsense mutation in two German patients with fucosidosis. Hum Mutat. 1995;6(2):184–185. doi: 10.1002/humu.1380060213. [DOI] [PubMed] [Google Scholar]
  16. Seo H. C., Kunze J., Willems P. J., Kim A. H., Hanefeld F., O'Brien J. S. A single-base deletion mutation in a Turkish patient with fucosidosis. Hum Mutat. 1994;3(4):407–408. doi: 10.1002/humu.1380030416. [DOI] [PubMed] [Google Scholar]
  17. Seo H. C., Willems P. J., Kretz K. A., Martin B. M., O'Brien J. S. Fucosidosis: four new mutations and a new polymorphism. Hum Mol Genet. 1993 Apr;2(4):423–429. doi: 10.1093/hmg/2.4.423. [DOI] [PubMed] [Google Scholar]
  18. Seo H. C., Willems P. J., O'Brien J. S. Six additional mutations in fucosidosis: three nonsense mutations and three frameshift mutations. Hum Mol Genet. 1993 Aug;2(8):1205–1208. doi: 10.1093/hmg/2.8.1205. [DOI] [PubMed] [Google Scholar]
  19. Seo H. C., Yang M., Tonlorenzi R., Willems P. J., Kim A. H., Filocamo M., Gatti R., DiCioccio R. A., O'Brien J. S. A missense mutation (S63L) in alpha-L-fucosidase is responsible for fucosidosis in an Italian patient. Hum Mol Genet. 1994 Nov;3(11):2065–2066. [PubMed] [Google Scholar]
  20. Taylor R. M., Farrow B. R., Stewart G. J. Amelioration of clinical disease following bone marrow transplantation in fucosidase-deficient dogs. Am J Med Genet. 1992 Feb 15;42(4):628–632. doi: 10.1002/ajmg.1320420439. [DOI] [PubMed] [Google Scholar]
  21. Taylor R. M., Farrow B. R., Stewart G. J. Correction of enzyme deficiency by allogeneic bone marrow transplantation following total lymphoid irradiation in dogs with lysosomal storage disease (fucosidosis). Transplant Proc. 1986 Apr;18(2):326–329. [PubMed] [Google Scholar]
  22. Taylor R. M., Farrow B. R., Stewart G. J., Healy P. J., Tiver K. The clinical effects of lysosomal enzyme replacement by bone marrow transplantation after total lymphoid irradiation on neurologic disease in fucosidase deficient dogs. Transplant Proc. 1988 Feb;20(1):89–93. [PubMed] [Google Scholar]
  23. Vellodi A., Cragg H., Winchester B., Young E., Young J., Downie C. J., Hoare R. D., Stocks R., Banerjee G. K. Allogeneic bone marrow transplantation for fucosidosis. Bone Marrow Transplant. 1995 Jan;15(1):153–158. [PubMed] [Google Scholar]
  24. Willems P. J., Darby J. K., DiCioccio R. A., Nakashima P., Eng C., Kretz K. A., Cavalli-Sforza L. L., Shooter E. M., O'Brien J. S. Identification of a mutation in the structural alpha-L-fucosidase gene in fucosidosis. Am J Hum Genet. 1988 Nov;43(5):756–763. [PMC free article] [PubMed] [Google Scholar]
  25. Willems P. J., Gatti R., Darby J. K., Romeo G., Durand P., Dumon J. E., O'Brien J. S. Fucosidosis revisited: a review of 77 patients. Am J Med Genet. 1991 Jan;38(1):111–131. doi: 10.1002/ajmg.1320380125. [DOI] [PubMed] [Google Scholar]
  26. Williamson M., Cragg H., Grant J., Kretz K., O'Brien J., Willems P. J., Young E., Winchester B. A 5' splice site mutation in fucosidosis. J Med Genet. 1993 Mar;30(3):218–223. doi: 10.1136/jmg.30.3.218. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES