Research Article

Norrie disease gene mutation in a large Costa Rican kindred with a novel phenotype including venous insufficiency

  1. Heidi L. Rehm1,2,
  2. Gustavo A. Gutiérrez-Espeleta3,
  3. Rafael Garcia4,
  4. Gerardo Jiménez5,
  5. Umang Khetarpal1,
  6. Janice M. Priest6,
  7. Katherine B. Sims7,
  8. Bronya J. B. Keats6,
  9. Cynthia C. Morton1,*

Article first published online: 7 JAN 1999

DOI: 10.1002/(SICI)1098-1004(1997)9:5<402::AID-HUMU4>3.0.CO;2-5

Issue

Human Mutation

Human Mutation

Volume 9, Issue 5, pages 402–408, 1997

Additional Information

How to Cite

Rehm, H. L., Gutiérrez-Espeleta, G. A., Garcia, R., Jiménez, G., Khetarpal, U., Priest, J. M., Sims, K. B., Keats, B. J. B. and Morton, C. C. (1997), Norrie disease gene mutation in a large Costa Rican kindred with a novel phenotype including venous insufficiency. Human Mutation, 9: 402–408. doi: 10.1002/(SICI)1098-1004(1997)9:5<402::AID-HUMU4>3.0.CO;2-5

Author Information

  1. 1

    Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

  2. 2

    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115

  3. 3

    Escuela de Biologia, Instituto de Investigaciones en Salud Universidad de Costa Rica, San José, Costa Rica

  4. 4

    Hospital México, CCSS, San José, Costa Rica

  5. 5

    Instituto de Investagaciones en Salud, Universidad de Costa Rica

  6. 6

    Department of Biometry and Genetics, Louisiana State University Medical Center, New Orleans, Louisiana 70112

  7. 7

    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115

*Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Publication History

  1. Issue published online: 7 JAN 1999
  2. Article first published online: 7 JAN 1999
  3. Manuscript Accepted: 16 APR 1996
  4. Manuscript Received: 1 MAR 1996

Funded by

  • Universidad de Costa Rica
  • NIH/NIDCD. Grant Numbers: DC00871, T32 HL07627

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Keywords:

  • Norrie disease;
  • venous insufficiency;
  • blindness;
  • deafness;
  • point mutation

Abstract

A large Costa Rican kindred has been identified with 15 males affected with congenital blindness, progressive hearing loss, and venous insufficiency. Due to ophthalmological and audio-otological findings, including bilateral retinal dysplasia and detachment, progressive bilateral sensorineural hearing loss, and an X-linked pattern of inheritance, a tentative diagnosis of Norrie disease was considered. However, venous insufficiency is a clinical finding not reportedly associated with Norrie disease. Genetic linkage analysis using microsatellite repeat markers demonstrated linkage to Xp11.23–11.4 (z = 2.723 at θ = 0.0). A candidate gene approach using the Norrie disease gene (NDP), which maps to Xp11.3, revealed a point mutation in the third exon resulting in substitution of phenylalanine for leucine at position 61. The precise function of the gene product, norrin, has yet to be elucidated; however, it has been postulated to be involved in the regulation or neural cell differentiation and proliferation, although hypotheses have been considered for its role in vascular development in the eye. The finding of a mutation in NDP in association with peripheral vascular disease may provide valuable insight into the potential role of this gene in cellular processes. Hum Mutat 9:402–408, 1997. © 1997 Wiley-Liss, Inc.

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