A novel splice acceptor site mutation which produces multiple splicing abnormalities resulting in protein S deficiency type I.
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.
Tatewaki
H
H
Department of Clinical Chemistry and Laboratory Medicine, Kyushu Faculty, University of Medicine, Fukuoka, Japan.
Iida
H
H
Nakahara
M
M
Tsuda
H
H
Kinoshita
S
S
Kanaji
T
T
Yoshida
N
N
Miyazaki
S
S
Hamasaki
N
N
D000293:Adolescent; D005260:Female; D006801:Humans; D009154:Mutation; D020151:Protein C Deficiency / Q000235:genetics*; D017293:Protein S / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*
D017293:Protein S