title: A novel splice acceptor site mutation which produces multiple splicing abnormalities resulting in protein S deficiency type I.
abstract: In an attempt to explore the molecular mechanisms for protein S deficiency, a patient with such a deficiency was examined at the DNA, RNA and protein levels. Nucleotide analyses revealed that the proband, the mother and the grandmother had a G-->C substitution in the invariant AG dinucleotide at the splicing acceptor site of intron A/exon 2. This patient was heterozygous for this substitution and the mutant allele was inherited from the proband's mother and grandmother. Reverse transcription-polymerase chain reaction analysis demonstrated several kinds of splicing abnormalities such as exon skipping and cryptic splicing, in addition to correct splicing. Semiquantitation of mRNA for the protein S gene revealed that the amount of the proband's mRNA was reduced to 60% of normal. Thus, this mutation impaired the normal processing of mRNA for the protein S gene, resulting in the subject's severe protein S deficiency.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tatewaki
authors.forename: H
authors.initials: H
authors.lastname: Iida
authors.forename: M
authors.initials: M
authors.lastname: Nakahara
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: S
authors.initials: S
authors.lastname: Kinoshita
authors.forename: T
authors.initials: T
authors.lastname: Kanaji
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
authors.forename: N
authors.initials: N
authors.lastname: Hamasaki
mesh_terms: D000293:Adolescent; D005260:Female; D006801:Humans; D009154:Mutation; D020151:Protein C Deficiency / Q000235:genetics*; D017293:Protein S / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*
chemical_list: D017293:Protein S