RESUMEN
Darier's disease is a rare autosomal dominant skin disorder in which there is abnormal adhesion between keratinocytes. It appears to be associated with an increased prevalence of neuropsychiatric disorders including mental retardation and epilepsy. In addition we have previously reported a family in which major affective disorder cosegregates with Darier's disease. In the present study we have localized the gene for Darier's disease to chromosome 12q23-q24.1 by linkage analysis in five British pedigrees. We obtained a maximum two point lod score of 4.29 with marker D12S84 at zero recombination fraction. All five families showed evidence of linkage between the disease gene and markers in this region. Subsequent identification of the Darier's disease gene will provide insights into normal mechanisms of cell adhesion and may be of importance in the genetic investigation of neuropsychiatric disorders as well as elucidating the pathogenesis of Darier's disease itself.
Asunto(s)
Cromosomas Humanos Par 12 , Enfermedad de Darier/genética , Mapeo Cromosómico , ADN/análisis , ADN/sangre , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , Linaje , Recombinación GenéticaRESUMEN
Munro and colleagues (Ann Génét, 1992, 35, 157-160) found small positive lod scores for linkage between the genes for Darier's disease and the Duffy blood locus in two large British families, with a maximum lod score in one family of 0.807 at theta = 0.0. The authors have examined five independent British pedigrees multiply affected by Darier's disease using highly polymorphic microsatellite DNA markers tightly linked to the Duffy locus. They were able to exclude close linkage between the Darier gene and CRP for theta < or = 0.16 and between the Darier gene and D1S104 for theta < or = 0.12. We conclude that the gene for Darier's disease does not lie close to the Duffy locus.