861 THE MOST FREQUENT HUMAN AUTOSOMAL RECESSIVE DISEASE

Abstract

Nonclassical steroid 21-hydroxylase deficiency (nc21OHD) is an autosomal recessive disease which results in a phenotypically variable syndrome of postnatal hyperandrogenism. Its prevalence is unknown because basal serum 17-OHP levels are not sufficiently elevated for detection with the microfilter paper technique used in screening for classical 21-OHD. We therefore ascertained the frequency of the nc21OHD gene using ethnic group-specific HLA-B-nc21OHD associations in conjunction with ACTH testing in obligate heterozygote parents. Confirmation of this approach was obtained by the affected sib pair method of Thomson and Bodmer. The gene frequency for nc21OHD was highest in Ashkenazi Jews (19.1%) and was also high in Hispanics (13.6%), Yugoslavs (12.5%), and Italians (5.8%). In other Caucasians studied it was 0.1%. Disease frequencies were 1/27 for Ashkenazi Jews, 1/53 for Hispanics, 1/63 for Yugoslavs, 1/333 for Italians, and 1/1000 for other Caucasians. Carriers of the HLA-B14 marker had a 32-fold increased risk of nc21OHD compared to controls. Linkage disequilibrium betweeen HLA-B14 and nc21OHD was significant in Ashkenazi Jewish, Hispanic, and Italian patients, but not in Yugoslavs or other Caucasians.Conclusion: It appears that nc21OHD is the most frequent autosomal recessive genetic disorder in man.