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

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

doi:10.1055/s-0037-1614631

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 82(01): 65-71
DOI: 10.1055/s-0037-1614631

Rapid Communication

Schattauer GmbH

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

Hideki Tatewaki

¹From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan

,

Hiroko Iida

¹From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan

,

Mutsuko Nakahara

¹From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan

,

Hiroko Tsuda

¹From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan

,

Sachiko Kinoshita

¹From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan

,

Taisuke Kanaji

¹From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan

,

Nobuyuki Yoshida

²From the Department of Pediatrics, Saga Medical College, Saga, Japan

,

Sumio Miyazaki

²From the Department of Pediatrics, Saga Medical College, Saga, Japan

,

Naotaka Hamasaki

¹From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan

› Institutsangaben

Abstract

Summary

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.

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Referenzen

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