Mucopolysaccharidosis type II (Hunter syndrome) : Mutation hot spots in the iduronate-2-sulfatase gene

• Published in: American journal of human genetics Vol. 59; no. 6; pp. 1202 - 1209
• Main Authors: RATHMANN, M, BUNGE, S, BECK, M, KRESSE, H, TYLKI-SZYMANSKA, A, GAL, A
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.12.1996
• Subjects: Alternative Splicing - genetics; Base Sequence; Biological and medical sciences; Carbohydrates (enzymatic deficiencies). Glycogenosis; Errors of metabolism; Female; Gene Rearrangement; Genetic Linkage; Genotype; Heterozygote; Humans; Iduronate Sulfatase - genetics; Male; Medical sciences; Metabolic diseases; Molecular Sequence Data; Mucopolysaccharidosis II - ethnology; Mucopolysaccharidosis II - genetics; Phenotype; Point Mutation - genetics; RNA, Messenger - genetics; X Chromosome - genetics; Human; Genetic inheritance; Enzyme; Family study; Diseases of the osteoarticular system; Metabolic diseases; Genotype; Esterases; Enzymopathy; Genetic disease; Hunter syndrome; Iduronate-2-sulfatase; Phenotype; Genetics; Hydrolases; Carbohydrate; Parental origin; Sulfuric ester hydrolases
• ISSN: 0002-9297; 1537-6605

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).