PHENOTYPIC VARIABILITY IN X-LINKED OCULAR ALBINISM - RELATIONSHIP TO LINKAGE GENOTYPES

One hundred nineteen individuals from 11 families with X-linked ocular albinism (OA1) were studied with respect to both their clinical pheno types and their linkage geno-types. In a four-generation Australian fa mily, two affected males and an obligatory carrier lacked cutaneous me lanin macroglobules (MMGs); ocular features were identical to those of Nettleship-Falls OA1. Four other families had more unusual phenotypic features in addition to OA1. All OA1 families were genotyped at DXS16 , DXS85, DXS143, STS, and DXS452 and for a CA-repeat polymorphism at t he Kallmann syndrome locus (KAL). Separate two-point linkage analyses were performed for the following: group A, six families with biopsy-pr oved MMGs in at least one affected male; group B, four families whose biopsy status was not known; and group C, OA-9 only (16 samples), the family without MMGs. At the set of loci closest to OA1, there is no cl ear evidence in our data set for locus heterogeneity between groups A and C or among the four other families with complex phenotypes. Combin ed multipoint analysis (LINKMAP) in the 11 families and analysis of in dividual recombination events confirms that the major locus for OA1 re sides within the DXS85-DXS143 interval. We suggest that more detailed clinical evaluations of OA1 individuals and families should be perform ed for future correlation with specific mutations in candidate OA1 gen es.