Original Investigation

Human Genetics

, Volume 107, Issue 3, pp 276-284

First online:

The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition

  • Sylvie GerberAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
  • , Jean-Michel RozetAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
  • , Shin-Ichiro TakezawaAffiliated withGraduate School for Biostudies, Kyoto, Japan
  • , Luisa Coutinho dos SantosAffiliated withServiço de Oftalmologia, Hospital Dos Capuchos, Lisboa, Portugal
  • , Lucilia LopesAffiliated withServiço de Oftalmologia, Hospital Dos Capuchos, Lisboa, Portugal
  • , Olivier GribouvalAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
  • , Clotilde PenetAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
  • , Isabelle PerraultAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
  • , Dominique DucroqAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
    • , Eric SouiedAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
    • , Marc JeanpierreAffiliated withINSERM U129 and Service de Biochimie et Génétique Moléculaire, Hôpital Cochin, Paris, France
    • , Serge RomanaAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
    • , Jean FrézalAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
    • , Fernando FerrazAffiliated withServiço de Genética, Hospital Dona Estefânia, Lisboa, Portugal
    • , Ruth Yu-UmesonoAffiliated withGraduate School for Biostudies, Kyoto, Japan
    • , Arnold MunnichAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France
    • , Josseline KaplanAffiliated withUnité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker, Paris, France

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Abstract.

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 at θ=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.