AUTOSOMAL RECESSIVE RETINITIS-PIGMENTOSA LOCUS MAPS ON CHROMOSOME 1Q IN A LARGE CONSANGUINEOUS FAMILY FROM PAKISTAN

A large Pakistani family with several consanguineous marriages is desc ribed, in which autosomal recessive retinitis pigmentosa is segregatin g. Linkage studies revealed close linkage between the disease locus an d six loci on chromosome 1q (D1S158, F13B, D1S422, D1S412, D1S413, and D1S53) with maximum lod scores ranging from 0.988-4.657 at Theta=0.06 5-0.235. However, the analysis of individual nuclear families showed v ery close linkage without recombination in three branches and several recombinants and negative lod scores throughout in the fourth branch. These results strongly suggest that mutations of two different genes a re responsible for the disease in the 'linked' and 'unlinked' branches . Parallel to the linkage heterogeneity, clear phenotypic differences have been observed among the 'linked' and 'unlinked' parts. Our findin gs demonstrate that in case of recessive disorders the possibility of non-allelic genetic heterogeneity should always be considered, even wi thin the same kindred and in genetic isolates if a largely extended pe digree is analysed.