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A Novel Splice Acceptor Site Mutation which Produces Multiple Splicing Abnormalities Resulting in Protein S Deficiency Type I

1999; Thieme Medical Publishers (Germany); Volume: 82; Issue: 07 Linguagem: Inglês

10.1055/s-0037-1614631

2567-689X

Hideki Tatewaki, Hiroko Iida, Mutsuko Nakahara, Hiroko Tsuda, Sachiko Kinoshita, Taisuke Kanaji, Nobuyuki Yoshida, Sumio Miyazaki, Naotaka Hamasaki,

Neurogenetic and Muscular Disorders Research

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.