Mucopolysaccharidosis type II (Hunter syndrome): mutation "hot spots" in the iduronate-2-sulfatase gene.
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-chromosomal storage disorder due to deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). We have identified IDS mutations in a total of 31 families/patients with MPS II, of which 20 are novel and unique and a further 1 is novel but has been found in 3 unrelated patients. One of the mutations detected is of special interest as an AG-->G substitution in an intron, far apart from the coding region, is deleterious by creating a new 5'-splice-donor site that results in the inclusion of a 78-bp intronic sequence. While the distribution of gene rearrangements (deletions, insertions, and duplications) of <20 bp seems to be random over the IDS gene, the analysis of a total of 101 point mutations lying within the coding region shows that they tend to be more frequent in exons III, VIII, and IX. Forty-seven percent of the point mutations are at CpG dinucleotides, of which G:C-to-A:T transitions constitute nearly 80%. Almost all recurrent point mutations involve CpG sites. Analysis of a collective of 50 families studied in our laboratory, to date, revealed that mutations occur more frequently in male meioses (estimated male-to-female ratio between 3.76 and 6.3).
Rathmann
M
M
Institut für Humangenetik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Bunge
S
S
Beck
M
M
Kresse
H
H
Tylki-Szymanska
A
A
Gal
A
A
D017398:Alternative Splicing / Q000235:genetics; D001483:Base Sequence; D005260:Female; D015321:Gene Rearrangement; D008040:Genetic Linkage; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016532:Mucopolysaccharidosis II / Q000208:ethnology / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
D012333:RNA, Messenger; D007066:Iduronate Sulfatase