title: Mutations affecting RNA splicing in man are detected more frequently in somatic than in germ cells.
abstract: The spectrum of DNA sequence alterations in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene of HPRTase-deficient T-lymphocytes isolated from the blood of healthy male donors was determined and compared with the spectrum found in patients suffering from genetic diseases (Lesch-Nyhan syndrome or gouty arthritis) associated with a mutation in the same gene. Most of the T-cell mutants still produced hprt mRNA which was converted into cDNA and used for DNA sequence analysis after amplification using the polymerase chain reaction (PCR). In 39% of the 31 analyzed T-cell mutants of normal donors 1 or 2 exons were completely or partially deleted from hprt mRNA, probably because of a mutation in a splice acceptor site. Among patients suffering from the Lesch-Nyhan syndrome or gouty arthritis, the class of splice mutations amounts only to 7%. These data suggest that carriers of splice mutations often do not show the characteristics of HPRTase deficiency associated with these genetic diseases, because correctly spliced hprt mRNA is still produced at a low level.
authors.affiliation: MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Rossi
authors.forename: J C
authors.initials: JC
authors.lastname: Thijssen
authors.forename: A D
authors.initials: AD
authors.lastname: Tates
authors.forename: H
authors.initials: H
authors.lastname: Vrieling
authors.forename: A T
authors.initials: AT
authors.lastname: Natarajan
authors.forename: P H
authors.initials: PH
authors.lastname: Lohman
authors.forename: A A
authors.initials: AA
authors.lastname: van Zeeland
mesh_terms: D015210:Arthritis, Gouty / Q000235:genetics*; D001483:Base Sequence; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D007926:Lesch-Nyhan Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase