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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1999 May;64(5):1394–1399. doi: 10.1086/302377

A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

M Kniazeva 1, M F Chiang 1, B Morgan 1, A L Anduze 1, D J Zack 1, M Han 1, K Zhang 1
PMCID: PMC1377876  PMID: 10205271

Abstract

Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4.

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Selected References

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  1. Allikmets R., Shroyer N. F., Singh N., Seddon J. M., Lewis R. A., Bernstein P. S., Peiffer A., Zabriskie N. A., Li Y., Hutchinson A. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science. 1997 Sep 19;277(5333):1805–1807. doi: 10.1126/science.277.5333.1805. [DOI] [PubMed] [Google Scholar]
  2. Allikmets R., Singh N., Sun H., Shroyer N. F., Hutchinson A., Chidambaram A., Gerrard B., Baird L., Stauffer D., Peiffer A. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet. 1997 Mar;15(3):236–246. doi: 10.1038/ng0397-236. [DOI] [PubMed] [Google Scholar]
  3. Bressler N. M., Bressler S. B., Fine S. L. Age-related macular degeneration. Surv Ophthalmol. 1988 May-Jun;32(6):375–413. doi: 10.1016/0039-6257(88)90052-5. [DOI] [PubMed] [Google Scholar]
  4. Cibis G. W., Morey M., Harris D. J. Dominantly inherited macular dystrophy with flecks (Stargardt). Arch Ophthalmol. 1980 Oct;98(10):1785–1789. doi: 10.1001/archopht.1980.01020040637010. [DOI] [PubMed] [Google Scholar]
  5. Deloukas P., Schuler G. D., Gyapay G., Beasley E. M., Soderlund C., Rodriguez-Tomé P., Hui L., Matise T. C., McKusick K. B., Beckmann J. S. A physical map of 30,000 human genes. Science. 1998 Oct 23;282(5389):744–746. doi: 10.1126/science.282.5389.744. [DOI] [PubMed] [Google Scholar]
  6. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  7. Evans K., Fryer A., Inglehearn C., Duvall-Young J., Whittaker J. L., Gregory C. Y., Butler R., Ebenezer N., Hunt D. M., Bhattacharya S. Genetic linkage of cone-rod retinal dystrophy to chromosome 19q and evidence for segregation distortion. Nat Genet. 1994 Feb;6(2):210–213. doi: 10.1038/ng0294-210. [DOI] [PubMed] [Google Scholar]
  8. Fish G., Grey R., Sehmi K. S., Bird A. C. The dark choroid in posterior retinal dystrophies. Br J Ophthalmol. 1981 May;65(5):359–363. doi: 10.1136/bjo.65.5.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fishman G. A. Fundus flavimaculatus. A clinical classification. Arch Ophthalmol. 1976 Dec;94(12):2061–2067. doi: 10.1001/archopht.1976.03910040721003. [DOI] [PubMed] [Google Scholar]
  10. Freund C. L., Gregory-Evans C. Y., Furukawa T., Papaioannou M., Looser J., Ploder L., Bellingham J., Ng D., Herbrick J. A., Duncan A. Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Cell. 1997 Nov 14;91(4):543–553. doi: 10.1016/s0092-8674(00)80440-7. [DOI] [PubMed] [Google Scholar]
  11. Hadden O. B., Gass J. D. Fundus flavimaculatus and Stargardt's disease. Am J Ophthalmol. 1976 Oct;82(4):527–539. doi: 10.1016/0002-9394(76)90539-0. [DOI] [PubMed] [Google Scholar]
  12. Hamajima N., Matsuda K., Sakata S., Tamaki N., Sasaki M., Nonaka M. A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution. Gene. 1996 Nov 21;180(1-2):157–163. doi: 10.1016/s0378-1119(96)00445-3. [DOI] [PubMed] [Google Scholar]
  13. Heiba I. M., Elston R. C., Klein B. E., Klein R. Sibling correlations and segregation analysis of age-related maculopathy: the Beaver Dam Eye Study. Genet Epidemiol. 1994;11(1):51–67. doi: 10.1002/gepi.1370110106. [DOI] [PubMed] [Google Scholar]
  14. Kaplan J., Gerber S., Larget-Piet D., Rozet J. M., Dollfus H., Dufier J. L., Odent S., Postel-Vinay A., Janin N., Briard M. L. A gene for Stargardt's disease (fundus flavimaculatus) maps to the short arm of chromosome 1. Nat Genet. 1993 Nov;5(3):308–311. doi: 10.1038/ng1193-308. [DOI] [PubMed] [Google Scholar]
  15. Kelsell R. E., Evans K., Gregory C. Y., Moore A. T., Bird A. C., Hunt D. M. Localisation of a gene for dominant cone-rod dystrophy (CORD6) to chromosome 17p. Hum Mol Genet. 1997 Apr;6(4):597–600. doi: 10.1093/hmg/6.4.597. [DOI] [PubMed] [Google Scholar]
  16. Kojima M., Hoshimaru M., Aoki T., Takahashi J. B., Ohtsuka T., Asahi M., Matsuura N., Kikuchi H. Expression of heat shock proteins in the developing rat retina. Neurosci Lett. 1996 Mar 1;205(3):215–217. doi: 10.1016/0304-3940(96)12406-x. [DOI] [PubMed] [Google Scholar]
  17. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am J Hum Genet. 1985 May;37(3):482–498. [PMC free article] [PubMed] [Google Scholar]
  18. Lopez P. F., Maumenee I. H., de la Cruz Z., Green W. R. Autosomal-dominant fundus flavimaculatus. Clinicopathologic correlation. Ophthalmology. 1990 Jun;97(6):798–809. doi: 10.1016/s0161-6420(90)32508-3. [DOI] [PubMed] [Google Scholar]
  19. MORTON N. E. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed] [Google Scholar]
  20. Mansour A. M. Long-term follow-up of dominant macular dystrophy with flecks (Stargardt). Ophthalmologica. 1992;205(3):138–143. doi: 10.1159/000310329. [DOI] [PubMed] [Google Scholar]
  21. Noble K. G., Carr R. E. Stargardt's disease and fundus flavimaculatus. Arch Ophthalmol. 1979 Jul;97(7):1281–1285. doi: 10.1001/archopht.1979.01020020023005. [DOI] [PubMed] [Google Scholar]
  22. Payne A. M., Downes S. M., Bessant D. A., Taylor R., Holder G. E., Warren M. J., Bird A. C., Bhattacharya S. S. A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1. Hum Mol Genet. 1998 Feb;7(2):273–277. doi: 10.1093/hmg/7.2.273. [DOI] [PubMed] [Google Scholar]
  23. Rebbe N. F., Hickman W. S., Ley T. J., Stafford D. W., Hickman S. Nucleotide sequence and regulation of a human 90-kDa heat shock protein gene. J Biol Chem. 1989 Sep 5;264(25):15006–15011. [PubMed] [Google Scholar]
  24. Seddon J. M., Ajani U. A., Mitchell B. D. Familial aggregation of age-related maculopathy. Am J Ophthalmol. 1997 Feb;123(2):199–206. doi: 10.1016/s0002-9394(14)71036-0. [DOI] [PubMed] [Google Scholar]
  25. Seddon J. M., Willett W. C., Speizer F. E., Hankinson S. E. A prospective study of cigarette smoking and age-related macular degeneration in women. JAMA. 1996 Oct 9;276(14):1141–1146. [PubMed] [Google Scholar]
  26. Small K. W., Syrquin M., Mullen L., Gehrs K. Mapping of autosomal dominant cone degeneration to chromosome 17p. Am J Ophthalmol. 1996 Jan;121(1):13–18. doi: 10.1016/s0002-9394(14)70529-x. [DOI] [PubMed] [Google Scholar]
  27. Stone E. M., Nichols B. E., Kimura A. E., Weingeist T. A., Drack A., Sheffield V. C. Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q. Arch Ophthalmol. 1994 Jun;112(6):765–772. doi: 10.1001/archopht.1994.01090180063036. [DOI] [PubMed] [Google Scholar]
  28. Stone E. M., Webster A. R., Vandenburgh K., Streb L. M., Hockey R. R., Lotery A. J., Sheffield V. C. Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration. Nat Genet. 1998 Dec;20(4):328–329. doi: 10.1038/3798. [DOI] [PubMed] [Google Scholar]
  29. Swain P. K., Chen S., Wang Q. L., Affatigato L. M., Coats C. L., Brady K. D., Fishman G. A., Jacobson S. G., Swaroop A., Stone E. Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration. Neuron. 1997 Dec;19(6):1329–1336. doi: 10.1016/s0896-6273(00)80423-7. [DOI] [PubMed] [Google Scholar]
  30. Young R. W. Pathophysiology of age-related macular degeneration. Surv Ophthalmol. 1987 Mar-Apr;31(5):291–306. doi: 10.1016/0039-6257(87)90115-9. [DOI] [PubMed] [Google Scholar]
  31. Zhang K., Bither P. P., Park R., Donoso L. A., Seidman J. G., Seidman C. E. A dominant Stargardt's macular dystrophy locus maps to chromosome 13q34. Arch Ophthalmol. 1994 Jun;112(6):759–764. doi: 10.1001/archopht.1994.01090180057035. [DOI] [PubMed] [Google Scholar]
  32. van Driel M. A., Maugeri A., Klevering B. J., Hoyng C. B., Cremers F. P. ABCR unites what ophthalmologists divide(s) Ophthalmic Genet. 1998 Sep;19(3):117–122. doi: 10.1076/opge.19.3.117.2187. [DOI] [PubMed] [Google Scholar]

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