Hunter syndrome among Jews in Israel.

Hunter syndrome (mucopolysaccharidosis II) is an X-linked lysosomal storage disorder caused by the deficiency of iduronate sulfatase (IDS), the gene of which is located at Xq28. A relatively high frequency of Hunter disease among Ashkenazi and Moroccan Jews in Israel was observed. Genetic analysis of the patients with Hunter disease in these ethnic groups indicated the absence of new mutations and a two-fold excess of individuals with the mutant allele over non carriers. This unusual phenomenon is unique to these ethnic groups and is suggestive of a prenatal selection process favoring the Hunter allele. Studies of the IDS gene structure and its flanking region are performed with the aim of detecting the mutations causing the disease in these patients and thus develop the most accurate diagnostic procedure for carrier identification among female relatives in these families. Furthermore, these studies are also aimed at identifying the unique molecular structure in the IDS gene or its flanking region which is the basis for the selection process. RFLP analysis using the cDNA gene (pc2S15) and DNA probes closely linked to the IDS gene, as well as the study of CA repeats in a closely linked region, indicated the absence of common haplotypes among Ashkenazi or Moroccan patients, excluding a linkage disequilibrium between a putative advantageous linked gene to the Hunter mutation in our patients. Studies of the IDS gene indicated a partial deletion in two patients while the other 12 patients had an apparent intact gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Mutation analysis of Jewish Hunter patients in Israel.

We have performed molecular and mutation analyses on 14 unrelated Israeli Hunter families and have identified the IDS mutation in 8 of them. Three unrelated Ashkenazi patients had the same previously reported mutation (1246 C-->T). Based on the haplotypes of the mutation-bearing chromosomes, we concluded that this is a recurrent mutation. In two patients, we identified a deletion spanning exons V-VII. Three novel mutations were observed in different patients: L410P, 717de14, and 244de13. In addition, the silent mutation (562 C-->T) was observed in one patient.

Combined enzymatic and linkage analysis for heterozygote detection in Hunter syndrome: identification of an apparent case of germinal mosaicism.

Hunter syndrome is an X-linked recessive disorder. Determination of heterozygotes is of vital importance in genetic counselling. We describe the DNA linkage analysis in 6 Hunter syndrome families and compare it to previous results based on a serum assay for IDS activity. Our results confirm the reliability of the serum assay. The serum test correctly detected 11/12 of the 1st degree relatives tested by the serum assay (6/7 carriers and 5/5 non-carriers). The only case with an apparent false negative result in the serum test was a daughter of a "probable heterozygote" whose serum test was also negative. We suggest that in this family the mother represented a case of germinal mosaicism and her daughter, based on the serum test, was not a carrier. If our interpretation is correct, then the apparent false negative results were correct. It is concluded that in families where the mutation is not known and DNA analysis is not possible due to the lack of informative RFLPs or due to the lack of DNA samples on key individuals, as well as in sporadic cases, the serum test should be applied as an alternative option for heterozygote detection.