A novel splice acceptor site mutation which produces multiple splicing abnormalities resulting in protein S deficiency type i
Tatewaki, H.; Iida, H.; Nakahara, M.; Tsuda, H.; Kinoshita, S.; Kanaji, T.; Yoshida, N.; Miyazaki, S.; Hamasaki, N.
Thrombosis and Haemostasis 82(1): 65-71
1999
ISSN/ISBN: 0340-6245 PMID: 10456456 Document Number: 510299
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.