Skip to main content
SpringerLink
Log in

Klinische und molekulargenetische Befunde bei einer Patientin mit Fundus albipunctatus

  • Kasuistik
  • Published:
Der Ophthalmologe Aims and scope Submit manuscript

Zusammenfassung

Methode

Die 38-jährige Indexpatientin wurde mittels Visus, Gesichtsfeld, Dunkeladaptation, Ophthalmoskopie, Elektroretinogramm (ERG) und multifokalem ERG untersucht. Die Exons 2–5 und die Exon-Intron-Übergänge des 11-cis-Retinoldehydrogenase-Gens wurden durch direkte Sequenzierung auf Mutationen geprüft.

Ergebnisse

Bei einem Visus von 1,0 zeigten sich parazentrale, mit Lesestörungen einhergehende Gesichtsfeldausfälle. Die Papillen waren regelrecht. Die Dunkeladaptation (DA) nach 45 min war stark vermindert. Das skotopische ERG nach 30 min DA zeigte verminderte Potenziale, nach 60 min DA jedoch eine fast normale Amplitudenhöhe. Im Zapfen-ERG waren grenzwertige 30 Hz-Flimmerlichtgipfelzeiten zu beobachten, jedoch keine Amplitudenreduktion. Im multifokalen ERG konnte eine retinale Ursache des parazentralen Gesichtsfeldausfalls nachgewiesen werden. Es wurden die für Fundus albipunctatus typischen Fundusveränderungen gefunden. Molekulargenetisch zeigte sich eine kombinierte Heterozygotie mit einer Ile33Asn- und einer Arg157Trp-Mutation.

Schlussfolgerungen

Die parazentralen Gesichtsfeldausfälle sind Folge einer Zapfenfunktionsstörung. Eine Zapfendystrophie lag bei unserer Patientin zumindest bisher nicht vor.

Abstract

Methods

The 38-year-old index patient was examined by visual acuity testing, perimetry, dark adaptometry, funduscopy, electroretinogram (ERG), and multifocal ERG. She was screened for mutations in exons 2–5 and exon/intron boundaries of the 11-cis retinol dehydrogenase gene by direct sequencing.

Results

Visual acuity was 1.0, but perimetry revealed paracentral scotomas associated with reading problems. The optic discs were normal. After 45 min of darkness there was nearly no increase of light sensitivity. After 30 min of dark adaptation, the scotopic ERG showed reduced amplitudes, but after 60 min a nearly normal level was reached. The 30-Hz flicker response of the cone ERG showed borderline implicit times, but no reduction of amplitudes. However, multifocal ERG clearly disclosed a paracentral amplitude reduction as the reason for the visual field defects. The fundus was typical for fundus albipunctatus. The patient is a compound heterozygote carrying a Ile33Asn and a Arg157Trp mutation.

Conclusions

The paracentral visual field defects were due to cone dysfunction. So far the patient exhibits no cone dystrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6a,b
Abb. 7a,b
Abb. 8

Literatur

  1. Cideciyan AV, Haeseleer F, Fariss RN, Aleman TS, Jang GF, Verlinde CL, Marmor MF, Jacobson SG, Palczewski K (2000) Rod and cone visual cycle consequences of a null mutation in the 11-cis retinol dehydrogenase gene in man. Vis Neurosci 17: 667–678

    Article  CAS  PubMed  Google Scholar 

  2. Driessen CAGG, Janssen APM, Winkens HJ, Vugt AHM van, Leeuw ALM de, Janssen JJM (1995) Cloning and expression of a cDNA encoding bovine retinal pigment epithelial 11-cis retinol dehydrogenase. Invest Ophthalmol Vis Sci 36: 1988–1996

    CAS  PubMed  Google Scholar 

  3. Driessen CAGG, Winkens HJ, Kuhlmann ED, Janssen APM, Vugt AHM van, Deutman AF, Janssen JJM (1998) The visual cycle retinol dehydrogenase: possible involvement in the 9-cis retinoic acid pathway. FEBS Letters 428: 135–140

    Article  CAS  PubMed  Google Scholar 

  4. Driessen CAGG, Winkens HJ, Hoffmann K, Kuhlmann ED, Janssen APM, Vugt AHM van, Hooser JP van, Wieringa BE, Deutman AF, Palczewski K, Ruether K, Janssen JJM (2000) Disruption of the 11-cis retinol dehydrogenase gene leads to accumulation of cis-retinols and cis-retinyl esters. Mol Cell Biol 20: 4275–4287

    Article  CAS  PubMed  Google Scholar 

  5. Driessen CAGG, Janssen APM, Winkens HJ, Kuhlmann ED, Vugt AHM van, Pinckers AJLG, Deutman AF, Janssen JJM (2001) Null mutation in the human 11-cis retinol dehydrogenase gene associated with fundus albipunctatus. Ophthalmology 108: 1479–1484

    Article  CAS  PubMed  Google Scholar 

  6. Gonzalez-Fernandez F, Kurz D, Bao Y, Newman S, Conway BP, Young JE, Han DP, Khani SC (1999) 11-cis Retinol dehydrogenase mutations as a major cause of the congenital night-blindness disorder known as fundus albipunctatus. Mol Vis 5: 41

    CAS  PubMed  Google Scholar 

  7. Hirose E, Inoue Y, Morimura H, Okamoto N, Fukuda M, Yamamoto S, Fujikado T, Tano Y (2000) Mutations in the 11-cis retinol dehydrogenase gene in Japanese patients with Fundus albipunctatus. Invest Ophthalmol Vis Sci 41: 3933–3935

    CAS  PubMed  Google Scholar 

  8. Jang GF, Van Hooser JP, Kuksa V, McBee JK, He YG, Janssen JJM, Driessen CAGG, Palczewski K (2001) Characterization of a dehydrogenase activity for oxidation of 11-cis-retinol in the retinal pigment epithelium of mice with a disrupted rdh5 gene: a model for the human hereditary disease fundus albipunctatus. J Biol Chem 276: 32.456–32.465

    Google Scholar 

  9. Kuroiwa S, Kikuchi T, Yoshimura N (2000) A novel compound heterozygous mutation in the rdh5 gene in a patient with fundus albipunctatus. Am J Ophthalmol 130: 672–675

    Article  CAS  PubMed  Google Scholar 

  10. Marmor MF, Zrenner E (1998, 1999 update) Standard for clinical electroretinography. International Society for Clinical Electrophysiology of Vision. Doc Ophthalmol 97: 143–156

    Google Scholar 

  11. McBee JK, Palczewski K, Baehr W, Pepperberg DR (2001) Confronting complexity: the interlink of phototransduction and retinoid metabolism in the vertebrate retina. Prog Retin Eye Res 20: 469–529

    Article  CAS  PubMed  Google Scholar 

  12. Nakamura M, Hotta Y, Tanikawa A, Terasaki H, Miyake Y (2000) A high association with cone dystrophy in fundus albipunctatus caused by mutations of the rdh5 gene. Invest Ophthalmol Vis Sci 41: 3925–3932

    CAS  PubMed  Google Scholar 

  13. Rattner A, Smallwood PM, Nathans J (2000) Identification and characterization of all-trans retinol dehydrogenase from photoreceptor outer segments, the visual cycle enzyme that reduces all-trans retinal to all-trans retinol. J Biol Chem 275: 11.034–11.043

    Article  Google Scholar 

  14. Shuber AP, Skoletsky J, Stern R, Handelin BL (1993) Efficient 12-mutation testing in the CFTR gene: a general method for complex mutation analysis. Hum Mol Genet 2: 153–158

    CAS  PubMed  Google Scholar 

  15. Simon A, Hellman U, Wernstedt C, Eriksson U (1995) The retinal pigment epithelial-specific 11-cis retinol dehydrogenase belongs to the family of short chain alcohol dehydrogenases. J Biol Chem 270: 1107–1112

    Article  CAS  PubMed  Google Scholar 

  16. Simon A, Lagercrantz J, Bajalica-Lagercrantz S, Eriksson U (1996) Primary structure of human 11-cis retinol dehydrogenase and organization and chromosomal localization of the corresponding gene. Genomics 36: 424–430

    Article  CAS  PubMed  Google Scholar 

  17. Wada Y, Abe T, Fuse N, Tamai M (2000) A frequent 1085delC/insGAAG mutation in the rdh5 gene in Japanese patients with fundus albipunctatus. Invest Ophthalmol Vis Sci 41: 1894–1897

    CAS  PubMed  Google Scholar 

  18. Wada Y, Abe T, Sato H, Tamai M (2001) A novel Gly35Ser mutation in the rdh5 gene in a Japanese family with fundus albipunctatus associated with cone dystrophy. Arch Ophthalmol 119: 1059–1063

    CAS  PubMed  Google Scholar 

  19. Wang J, Chai X, Eriksson U, Napoli JL (1999) Activity of human 11-cis retinol dehydrogenase (rdh5) with steroids and retinoids and expression of its mRNA in extra-ocular human tissue. Biochem J 338: 23–27

    Article  CAS  PubMed  Google Scholar 

  20. Yamamoto H, Simon A, Eriksson U Harris E, Berson EL, Dryja TP (1999) Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet 22: 188–191

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Charité, Universitätsmedizin Berlin, Augenklinik Campus Virchow Klinikum

    K. Rüther, M. Bohne & J. Reimann

  2. Augenklinik, Universität Nijmegen

    B. P. M. Janssen & J. J. M. Janssen

  3. Charité, Universitätsmedizin Berlin, Augenklinik Campus Benjamin Franklin

    U. Kellner

  4. Department of Biochemistry, Universität Nijmegen

    C. A. G. G. Driessen

  5. Charité-Virchow Augenklinik, Humboldt-Universität Berlin, Augustenburger Platz 1, 13353 , Berlin

    K. Rüther

Authors
  1. K. Rüther
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. P. M. Janssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. Kellner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. J. M. Janssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Bohne
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Reimann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. A. G. G. Driessen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Rüther.

Additional information

Teile des Beitrags wurden als Vortrag auf der 100. Tagung der Deutschen Ophthalmologischen Gesellschaft gehalten.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rüther, K., Janssen, B.P.M., Kellner, U. et al. Klinische und molekulargenetische Befunde bei einer Patientin mit Fundus albipunctatus. Ophthalmologe 101, 177–185 (2004). https://doi.org/10.1007/s00347-003-0895-y

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00347-003-0895-y

Schlüsselwörter

Keywords

Search

Navigation