Human Genetics

, Volume 108, Issue 1, pp 51–54

Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America

  • M. Bassi
  • Arthur Bergen
  • Pierre Bitoun
  • Stephen Charles
  • Maurizio Clementi
  • Richard Gosselin
  • Jane Hurst
  • Richard Lewis
  • Birgit Lorenz
  • Thomas Meitinger
  • Ludwine Messiaen
  • Rajkumar Ramesar
  • Andrea Ballabio
  • M. Schiaffino
Original Investigation

DOI: 10.1007/s004390000440

Cite this article as:
Bassi, M., Bergen, A., Bitoun, P. et al. Hum Genet (2001) 108: 51. doi:10.1007/s004390000440

Abstract.

Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G protein-coupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder.

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • M. Bassi
    • 1
  • Arthur Bergen
    • 2
  • Pierre Bitoun
    • 3
  • Stephen Charles
    • 4
  • Maurizio Clementi
    • 5
  • Richard Gosselin
    • 6
  • Jane Hurst
    • 7
  • Richard Lewis
    • 8
  • Birgit Lorenz
    • 9
  • Thomas Meitinger
    • 10
  • Ludwine Messiaen
    • 11
  • Rajkumar Ramesar
    • 12
  • Andrea Ballabio
    • 1
  • M. Schiaffino
    • 1
  1. 1.Telethon Institute of Genetics and Medicine (TIGEM), 20132 Milan, Italy
  2. 2.The Netherlands Ophthalmic Research Institute, 1100 AC Amsterdam, The Netherlands
  3. 3.Medical Genetics, CHU Paris-Nord, Jean Verdier Hospital, Bondy 93143 Cedex, France
  4. 4.Manchester Royal Eye Hospital, Manchester, M13 9WH, UK
  5. 5.Medical Genetics, Department of Pediatrics, University of Padua, 35128 Padua, Italy
  6. 6.Centre de Medecine Familiale de Granby, Granby, Quebec J2G 4Y5, Canada
  7. 7.Clinical Genetics, The Churchill, Oxford Radcliffe NHS Trust, Oxford OX3 7LJ, UK
  8. 8.Departments of Ophthalmology, Medicine, Pediatrics, and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
  9. 9.Department of Pediatric Ophthalmology and Ophthalmogenetics, Klinikum, Regensburg University, 93042 Regensburg, Germany
  10. 10.Abteilung fur Padiatrische Genetik, Kinderpoliklinik der Ludwig-Maximilians-Universitat, 80336 Munich, Germany
  11. 11.Department of Medical Genetics, University Hospital, 9000 Ghent, Belgium
  12. 12.Department of Human Genetics, University of Cape Town Medical School, Observatory 7925, South Africa
  13. 13.Universita' Vita-Salute San Raffaele, 20132 Milan, Italy
  14. 14.Present address: TIGEM, 80131 Naples, Italy
  15. 15.Present address: TIGEM and Seconda Universita' di Napoli, 80131 Naples, Italy
  16. 16.Present address: DIBIT, Scientific Institute San Raffaele, Via Olgettina 58, 20132 Milan, Italy, e-mail: schiaffino.mariavittoria@hsr.it, Tel.: +39-02-2643-4734, Fax: +39-02-2643-4723