X-LINKED HUNTER SYNDROME - HETEROZYGOUS PHENOTYPE IN CELL-CULTURE

Abstract

Fibroblast cultures derived from the skin of 3 Hunter heterozygotes were examined for iduronate sulfatase deficiency primarily by measurement of 35S-mucopolysaccharide accumulation in the presence and absence of Hunter corrective factor. For each heterozygote, 2 populations of clones were observed: normal and enzyme deficient, as predicted by the Lyon hypothesis. The phenotype of the uncloned cultures was usually normal, presumably because of cross-correction, even after storage in liquid N2. Mixing experiments indicate that the presence of a majority of cells with the Hunter phenotype may be obscured as the result of correction by the minority population of normal cells in the mixture. Variability in the ability to cross-correct was also demonstrated. The unpredictable behavior of uncloned cultures makes them unsuitable for diagnosing the Hunter carrier state.