title: Detection of point mutations and a gross deletion in six Hunter syndrome patients.
abstract: We have used screening with the polymerase chain reaction and chemical mismatch detection of amplified cDNA to detect and characterize deletions and point mutations in six Hunter Syndrome patients. A high degree of mutational heterogeneity was observed. The first patient is completely deleted for the gene coding for alpha-L-iduronate sulfate sulfatase, while the second has a point mutation that creates a stop codon. The third patient shows a point mutation that creates a novel splice site that is preferentially utilized and results in partial loss of one exon in the RNA. Patients 4, 5, and 6 have point mutations resulting in single amino acid substitutions. Four of the six single-base changes observed in this study were examples of transitions of the highly mutable dinucleotide CpG to TpG. This study has demonstrated a procedure capable of detecting all types of mutation that affect the function of the IDS protein and should enable direct carrier and prenatal diagnosis for Hunter syndrome families.
authors.affiliation: Paediatric Research Unit, United Medical School, Guy's Hospital, London, United Kingdom.
authors.forename: R H
authors.initials: RH
authors.lastname: Flomen
authors.forename: P M
authors.initials: PM
authors.lastname: Green
authors.forename: D R
authors.initials: DR
authors.lastname: Bentley
authors.forename: F
authors.initials: F
authors.lastname: Giannelli
authors.forename: E P
authors.initials: EP
authors.lastname: Green
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002872:Chromosome Deletion; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics; D008969:Molecular Sequence Data; D016532:Mucopolysaccharidosis II / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D004247:DNA; D007066:Iduronate Sulfatase