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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
1   From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan
,
Hiroko Iida
1   From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan
,
Mutsuko Nakahara
1   From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan
,
Hiroko Tsuda
1   From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan
,
Sachiko Kinoshita
1   From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan
,
Taisuke Kanaji
1   From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan
,
Nobuyuki Yoshida
2   From the Department of Pediatrics, Saga Medical College, Saga, Japan
,
Sumio Miyazaki
2   From the Department of Pediatrics, Saga Medical College, Saga, Japan
,
Naotaka Hamasaki
1   From the Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan
› Author AffiliationsWe wish to thank Professor Sheshadri Narayanan, New York Medical College (USA), and Dr. Lesly Bruce, Bristol University (UK), for critical reading of this manuscript. This work was supported in part by Grant-in Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and by P & P Grant from Kyushu University to NH.
Further Information

Publication History

Received 31 December 1998

Accepted after revision 12 April 1999

Publication Date:
11 December 2017 (online)

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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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