The last Crypto-Jews (Marranos) are the survivors of Spanish Jews who were persecuted in the late fifteenth century, escaped to Portugal and were forced to convert to save their lives. Isolated groups still exist in mountainous areas such as Belmonte in the Beira-Baixa province of Portugal. We report here the genetic study of a highly consanguineous endogamic population of Crypto-Jews of Belmonte affected with autosomal recessive retinitis pigmentosa (RP). A genome-wide search for homozygosity allowed us to localize the disease gene to chromosome 15q22-q24 (Zmax=2.95 atθ=0 at the D15S131 locus). Interestingly, the photoreceptor cell-specific nuclear receptor (PNR) gene, the expression of which is restricted to the outer nuclear layer of retinal photoreceptor cells, was found to map to the YAC contig encompassing the disease locus. A search for mutations allowed us to ascribe the RP of Crypto-Jews of Belmonte to a homozygous missense mutation in the PNR gene. Preliminary haplotype studies support the view that this mutation is relatively ancient but probably occurred after the population settled in Belmonte.

Authors and Affiliations

1. Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France, , , , ,

   Sylvie Gerber, Jean-Michel Rozet, Olivier Gribouval, Clotilde Penet, Isabelle Perrault, Dominique Ducroq, Eric Souied, Serge Romana, Jean Frézal, Arnold Munnich & Josseline Kaplan

2. Graduate School for Biostudies, Kyoto, Japan, , , , ,

   Shin-Ichiro Takezawa & Ruth Yu-Umesono

3. Serviço de Oftalmologia, Hospital Dos Capuchos, Lisboa, Portugal, , , , ,

   Luisa Coutinho dos Santos & Lucilia Lopes

4. INSERM U129 and Service de Biochimie et Génétique Moléculaire, Hôpital Cochin, Paris, France, , , , ,

   Marc Jeanpierre

5. Serviço de Genética, Hospital Dona Estefânia, Lisboa, Portugal, , , , ,

   Fernando Ferraz

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