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Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype–phenotype correlations and impact on genetic counseling†‡

  1. Valérie Pelletier1,
  2. Marguerite Jambou1,
  3. Nathalie Delphin1,
  4. Elena Zinovieva1,
  5. Morgane Stum1,
  6. Nadine Gigarel1,
  7. Hélène Dollfus2,
  8. Christian Hamel3,
  9. Annick Toutain4,
  10. Jean-Louis Dufier5,
  11. Olivier Roche5,
  12. Arnold Munnich1,
  13. Jean-Paul Bonnefont1,
  14. Josseline Kaplan1,*,
  15. Jean-Michel Rozet1

Article first published online: 12 SEP 2006

DOI: 10.1002/humu.20417

Issue

Human Mutation

Human Mutation

Volume 28, Issue 1, pages 81–91, January 2007

Additional Information

How to Cite

Pelletier, V., Jambou, M., Delphin, N., Zinovieva, E., Stum, M., Gigarel, N., Dollfus, H., Hamel, C., Toutain, A., Dufier, J.-L., Roche, O., Munnich, A., Bonnefont, J.-P., Kaplan, J. and Rozet, J.-M. (2007), Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype–phenotype correlations and impact on genetic counseling. Human Mutation, 28: 81–91. doi: 10.1002/humu.20417

Author Information

  1. 1

    Unité de Recherches Génétique et Epigénétique des Maladies Métaboliques, neurosensorielles et du Développement; Institut Nationale de la Santé et de la Recherche Médicale (INSERM) U781, Hôpital Necker–Enfants Malades, Paris, France

  2. 2

    Service de Génétique Médicale, Hôpital de Haute-Pierre, Strasbourg, France

  3. 3

    Unité INSERM 583, Hôpital Saint-Eloi, Montpellier, France

  4. 4

    Service de Génétique Médicale, Centre Hospitalo-Universitaire, Tours, France

  5. 5

    Servive d'Ophtalmologie, Hôpital Necker–Enfants Malades, Paris, France

*Unité de Recherches Génétique et Epigénétique des Maladies Métaboliques, neurosensorielles et du Développement. INSERM U781. Hôpital Necker–Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France

  1. †

    Communicated by Daniel F. Schorderet

  2. ‡

    Valérie Pelletier and Marguerite Jambou contributed equally to this work.

Publication History

  1. Issue published online: 7 DEC 2006
  2. Article first published online: 12 SEP 2006
  3. Manuscript Accepted: 25 JUL 2006
  4. Manuscript Received: 27 APR 2006

Funded by

  • Association Retina France

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Keywords:

  • retinitis pigmentosa;
  • RP;
  • X-linked;
  • XLRP;
  • cone dystrophy;
  • RP2;
  • RPGR

Abstract

X-linked forms of retinitis pigmentosa (RP) (XLRP) account for 10 to 20% of families with RP and are mainly accounted for by mutations in the RP2 or RP GTPase regulator (RPGR) genes. We report the screening of these genes in a cohort of 127 French family comprising: 1) 93 familial cases of RP suggesting X-linked inheritance, including 48 out of 93 families with expression in females but no male to male transmission; 2) seven male sibships of RP; 3) 25 sporadic male cases of RP; and 4) two cone dystrophies (COD). A total of 5 out of the 93 RP families excluded linkage to the RP2 and RP3 loci and were removed form the cohort. A total of 14 RP2 mutations, 12 of which are novel, were identified in 14 out of 88 familial cases of RP and 1 out of 25 sporadic male case (4%). In 13 out of 14 of the familial cases, no expression of the disease was noted in females, while in 1 out of 14 families one woman developed RP in the third decade. A total of 42 RPGR mutations, 26 of which were novel, were identified in 80 families, including: 69 out of 88 familial cases (78.4%); 2 out of 7 male sibship (28.6%); 8 out of 25 sporadic male cases (32.0%); and 1 out of 2 COD. No expression of the disease was noted in females in 41 out of 69 familial cases (59.4%), while at least one severely affected woman was recognized in 28 out of 69 families (40.6%). The frequency of RP2 and RPGR mutations in familial cases of RP suggestive of X-linked transmission are in accordance to that reported elsewhere (RP2: 15.9% vs. 6–20%; RPGR: 78.4% vs. 55–90%). Interestingly, about 30% of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30 years. Hum Mutat 28(1), 81–91, 2007. © 2006 Wiley-Liss, Inc.

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