Genetics of Hunter syndrome: carrier detection, new mutations, segregation and linkage analysis.

We have investigated 31 families segregation for Hunter Syndrome in order to advance our understanding of the genetics of this disease. The hair root test for the diagnosis of carriers of Hunter Syndrome was improved by the adoption of a new diagnostic index that distinguishes between carrier and normal females better than previous methods of analysis. One hundred and eleven female relatives of the affected children were tested by such procedures. This showed that seven out of 31 mothers were not carriers (22.6%), thus suggesting a small deficit of new mutation relative to the expectation that 33% of lethal, recessive alleles arise anew in a population at equilibrium at a sex-linked locus with equal mutation rates in male and female gametogenesis. The difference, however, is not statistically significant. The age of the parents of new mutants was slightly but significantly raised. Nevertheless, the independent increase in the age of the fathers of new female mutants was not statistically significant. Finally, a deficit of affected males was observed. This was significant and suggests the possibility of intrauterine loss of some affected males. Linkage analysis between the Hunter Syndrome locus, three polymorphisms in the Factor IX gene and the anonymous polymorphic probes 52A and DX13 showed that the Hunter locus is fairly closely linked to DX13, and hence distal to the Factor IX gene, while no linkage was observed with the 52A polymorphic site. The maximum lod score for the linkage between factor IX and the Hunter Syndrome locus was 0.424 at theta = 0.25; and that for the linkage between the Hunter Syndrome locus and DX13 was 3.01 at theta = 0.1.