title: Analysis for heterozygosity of protein S mRNA: application to genetic screening and family studies in hereditary protein S deficiency.
abstract: We genetically screened patients with hereditary protein S deficiency for heterozygosity of protein S mRNA using PCR-RFLP for Pro626 polymorphism. All patients who showed hemizygous state of protein S mRNA, characterized by markedly decreased levels of one allele, had a phenotype of type I protein S deficiency. A putative mutation, such as a nonsense or splice site mutation, in the silent alleles may have affected the mutated mRNA metabolism and reduced the mutated mRNA accumulation, and consequently resulted in type I protein S deficiency in these patients. We also applied this mRNA-based analysis to family studies in hereditary protein S deficiency. In a family with type I protein S deficiency, all affected individuals showed a loss of one allele at the mRNA level and the silent allele cosegregated with the disease phenotype. Detection of hemizygous expression of protein S mRNA provided direct evidence for type I protein S deficiency without further precise genetic analysis. Our findings indicate that this mRNA-based analysis can be a useful strategy for genetic screening and family studies in hereditary protein S deficiency.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: J
authors.initials: J
authors.lastname: Takamatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: A
authors.initials: A
authors.lastname: Katsumi
authors.forename: K
authors.initials: K
authors.lastname: Kagami
authors.forename: I
authors.initials: I
authors.lastname: Sugiura
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017293:Protein S / Q000235:genetics*; D018455:Protein S Deficiency / Q000175:diagnosis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D003062:Codon; D017293:Protein S; D012333:RNA, Messenger