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Article
February 1996

Linkage of Autosomal Dominant Radial Drusen (Malattia Leventinese) to Chromosome 2p16-21

Author Affiliations

From the Hôpital Jules Gonin (Drs Héon, Piguet, and Munier) and the Department of Genetic Medicine, Centre Hospitalier Universitaire Vaudois (Drs Héon, Munier, Pescia, and Schorderet), Lausanne, Switzerland; Department of Ophthalmology, University of Toronto, Toronto, Ontario (Dr Héon); and Departments of Ophthalmology (Mss Taylor, Streb, and Wiles and Dr Stone) and Pediatrics (Drs Nishimura and Sheffield), The University of Iowa, Iowa City. Drs Sneed (Phoenix, Ariz), Morgan (Huntington, WVa), and Forni (Bellinzona, Ticino, Switzerland) are ophthalmologists in private practice.

Arch Ophthalmol. 1996;114(2):193-198. doi:10.1001/archopht.1996.01100130187014
Abstract

Objective:  To identify the chromosomal location of the gene involved in the pathogenesis of autosomal dominant radial drusen (malattia leventinese).

Patients:  Eighty-six members of four families affected with radial drusen; one family of American origin and three families of Swiss origin.

Methods:  Family members were clinically examined for the presence of radial drusen. Affected patients and potentially informative spouses were genotyped with short tandem repeat polymorphisms distributed across the autosomal genome. The clinical and genotypic data were subjected to linkage analysis.

Results:  Fifty-six patients were found to be clinically affected. Significant linkage was observed between the disease phenotype and markers known to lie on the short arm of chromosome 2. The maximum two-point lod score (Zmax) observed for all four families combined was 10.5 and was obtained with marker D2S378. Multipoint analysis yielded a Zmax of 12, centered on marker D2S378. The lod-1 confidence interval was 8 cM, while the disease interval defined by observed recombinants was 14 cM.

Conclusions:  The gene responsible for autosomal dominant radial drusen has been mapped to the short arm of chromosome 2. This is an important step toward actually isolating the disease-causing gene. In addition, this information can be used to evaluate other familial drusen phenotypes such as Doyne's macular dystrophy for a possible allelic relationship.

References
1.
Best F.  Ueber eine hereditäre Maculaaffektion: Beitrag zur Vererbungslehre . Z Augenheilkd . 1905;13:199-212.
2.
Sorsby A, Joll Mason ME, Gardener N.  A fundus dystrophy with unusual features . Br J Ophthalmol . 1949;33:67-97.Article
3.
Stargardt K.  Ueber familiare, progressive Degeneration in der Makulagegend des Auges . Albrecht Graef Arch Klin Exp Ophthalmol . 1909;71:534-550.Article
4.
Ferrell RE, Mintz-Hittner H, Antoszyk JH.  Linkage of atypical vitelliform macular dystrophy (VMD-1) to the soluble glutamate pyruvate transaminase (GPT1) locus . Am J Hum Genet . 1983;35:78-84.
5.
Jacobson DM, Thompson HS, Bartley JA.  X-linked progressive cone dystrophy . Ophthalmology . 1989;96:885-895.Article
6.
Small KW, Weber JL, Roses A, et al.  North Carolina macular dystrophy is assigned to chromosome 6 . Genomics . 1992;13:681-685.Article
7.
Stone EM, Nichols BE, Streb LM, Kimura AE, Sheffield VC.  Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13 . Nature Genet . 1992;1:246-250.Article
8.
Forsman K, Graff C, Nordstrom S, et al.  The gene for Best's macular dystrophy is located in 11q13 in a Swedish family . Clin Genet . 1992;42:156-159.Article
9.
Kaplan JS, Gerber S, Lavget-Piet D, et al.  A gene for Stargardt's disease (fundus flavimaculatus) maps to the short arm of chromosome 1 . Nature Genet . 1993;5:308-311.Article
10.
Stone EM, Nichols BE, Kimura AE, et al.  Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q . Arch Ophthalmol . 1994;112:763-772.Article
11.
Zhang K, Bither PP, Park R, et al.  A dominant Stargardt's macular dystrophy locus maps to chromosome 13q34 . Arch Ophthalmol . 1994;112:759-764.Article
12.
Evans K, Fryer A, Inglehearn C, et al.  Genetic linkage of cone-rod retinal dystrophy to chromosome 19q and evidence for segregation distortion . Nature Genet . 1994;6:210-213.Article
13.
Kremer H, Pinckers A, van den Helm B, et al.  Localization of the gene for dominant cystoid macular dystrophy on chromosome 7p . Hum Mol Genet . 1994;3:299-302.Article
14.
Kelsell RE, Godley BF, Evans K, et al.  Localization of the gene for progressive bifocal chorioretinal atrophy (PBCRA) to chromsome 6q . Hum Mol Genet . 1995;4:1653-1656.Article
15.
Nathans J, Davenport CM, Maumenee IH, et. al.  Molecular genetics of human blue cone monochromacy . Science . 1989;245:831-838.Article
16.
Wells J, Wroblewski J, Keen J.  Mutations in the human retinal degeneraton slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy . Nature Genet . 1993;3:213-218.Article
17.
Nichols BE, Sheffield VC, Vandenburgh K.  Butterfly-shaped pigment dystrophy of the fovea is caused by a point mutation in codon 167 of the RDS gene . Nature Genet . 1993a;3:202-207.Article
18.
Weber BHF, Vogt G, Pruett RC, Stohr H, Felbor U.  Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy . Nature Genet . 1994;8:352-355.Article
19.
Leibowitz H, Krueger DE, Maunder LR, et al.  The Framington Eye Study Monograph: an ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration and visual acuity in a general population of 2631 adults, 1973-75 . Surv Ophthalmol . 1980;24( (suppl) ):335-610.Article
20.
Hutchinson J, Tay W.  Symmetrical central choroidoretinal disease occurring in senile persons . R Lond Ophthalmol Hosp Rep . 1875;8:231-244.
21.
Doyne RW.  Peculiar condition of choroiditis occurring in several members of the same family . Trans Ophthalmol Soc U K . 1899;19:71.
22.
Collins T.  A pathological report upon a case of Doyne's choroiditis ('honey-comb' or 'family choroiditis') . Ophthalmoscope . 1913;11:537-538.
23.
Vogt A.  Die Ophthalmoskopie im rotfreien Licht . In: Graefe Saemisch Hand-buch der Gesamten Augenheilkunde . 3rd ed. Berlin, Germany: Springer; 1925;3:1-118.
24.
Klainguti R.  Die Tapeto-retinal Degeneration im Kanton Tessin . Klin Monatsbl Augenheilkd . 1932;89:253-254.
25.
Waardenburg PJ.  On macula-degeneration . Ophthalmologica . 1948;115:115-116.
26.
Forni S, Babel J.  Étude clinique et histologique de la malattia leventinse: affection appartenant au groupe des dégénérescences hyalines du pôle postérieur . Ophthalmologica . 1962;143:313-322.Article
27.
Piguet B, Haimovici R, Bird AC.  Dominantly inherited drusen represent more than one disorder: a historical review . Eye . 1995;9:34-41.Article
28.
Streicher T, Kremery K.  Das fluoreszenzangiographische Bild der hereditären Drusen . Klin Monatsbl Augenheilkd . 1976;169:22-30.
29.
Dusek J, Streicher T, Schmidt K.  Hereditäre Drusen der Bruchschen Membran, I: klinische und lichtmikroskopische Beobachtungen . Klin Monatsbl Augenheilkd . 1982;181:27-31.Article
30.
Gass JDM.  Diseases causing choroidal exudative and hemorrhagic localized (disciform) detachment of the retina and pigment epithelium . In: Stereoscopic Atlas of Macular Diseases . St Louis, Mo: CV Mosby Co; 1987;3:96-97.
31.
Scarpatetti A, Forni S, Niemeyer G.  Die Netzhautfunktion bei Malattia leventinese (dominant Drusen) . Klin Monatsbl Augenheilkd . 1978;4:590-597.
32.
Buffone GJ, Darlington GJ.  Isolation of DNA from biological specimens without extraction with phenol . Clin Chem . 1985;31:164-165.
33.
Sheffield VC, Weber JL, Buetow KL, et al.  A collection of tri- and tetranucleotide repeat markers used to generate high quality, high resolution human genomewide linkage maps . Hum Molec Genet . 1995;4:1837-1844.Article
34.
Bassam B J, Caetano-Anolles G, Gresshoff PM.  Fast and sensitive silver staining of DNA in polyacrylamide gels . Anal Biochem . 1991;196:80-83.Article
35.
Nichols BE, Bascom R, Litt M, et al.  Refining the locus for Best's vitelliform macular dystrophy and mutation analysis of the candidate gene ROM1 . Am J Hum Genet . 1994;54:95-103.
36.
Cottingham Jr RW, Idury RM, Schaffer AA.  Faster sequential genetic linkage computations . Am J Hum Genet . 1993;53:252-263.
37.
Schaffer AA, Gupta SK, Shriram K, Cottingham RW Jr.  Avoiding recomputation in genetic linkage analysis . Hum Hered . 1994;44:225-237.Article
38.
Lathrop GM, Lalouel JM.  Easy calculations of lod scores and genetic risks on small computers . Am J Hum Genet . 1984;36:460-465.
39.
Donis-Keller H, Green P, Helms C, et al.  A genetic linkage map of the human genome . Cell . 1987;51:319-337.Article
40.
Conneally PM, Edwards JH, Kidd KK, et al.  Report of the Committee on Methods of Linkage Analysis and Reporting . Cytogenet Cell Genet . 1985;40:356-359.Article
41.
Gass JDM.  Drusen and disciform macular detachment and degeneration . Arch Ophthalmol . 1973;90:206-217.Article
42.
Hyman LG, Lilienfeld AM, Ferris FL, Fine SL.  Senile macular degeneration: a case-control study . Am J Epidemiol . 1983;118:213-227.
43.
Heiba IM, Elston RC, Klein BEK, Klein R.  Sibling correlations and segregation analysis of age-related maculopathy: the Beaver Dam Eye Study . Genet Epidemiol . 1994;11:51-67.Article
44.
Hu RJ, Watanabe M, Bennett V.  Characterization of human brain cDNA encoding the general insoform of β-spectrin . J Biol Chem . 1992;267:18715-18722.
45.
Chang JG, Scarpa A, Eddy RL, et al.  Cloning of a portion of the chromosomal gene and cDNA for human β-fodrin, the nonerythroid form of β-spectrin . Genomics . 1993;17:287-293.Article
46.
Travis G, Sutcliffe J, Bok D.  The retinal degeneration slow (rds) gene product is a photoreceptor disc membrane-associated glycoprotein . Neuron . 1991;6:61-70.Article
47.
Bascom RA, Schappert K, Mclnnes RR.  Cloning of the human and murine ROM 1genes: genomic organization and sequence conservation . Hum Molec Genet . 1993;2:385-391.Article
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