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

The last Crypto-Jews (Marranos) are the survivors of Spanish Jews who were persecuted in the late fifteenth century, escaped to Portugal and were forc ed to convert to save their lives. Isolated groups still exist in mountaino us areas such as Belmonte in the Beira-Baixa province of Portugal. We repor t here the genetic study of a highly consanguineous endogamic population of Crypto-Jews of Belmonte affected with autosomal recessive retinitis pigmen tosa (RP). A genome-wide search for homozygosity allowed us to localize the disease gene to chromosome 15q22-q24 (Zmax=2.95 at theta-0 at the D15S131 locus). Interestingly, the photoreceptor cell-specific nuclear receptor (PN R) gene, the expression of which is restricted to the outer nuclear layer o f retinal photoreceptor cells, was found to map to the YAC contig encompass ing 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 gen e. Preliminary haplotype studies support the view that this mutation is rel atively ancient but probably occurred after the population settled in Belmo nte.