A novel frameshift mutation in exon 4 causing a deficiency of high-molecular-weight kininogen in a patient with splenic infarction.
High-molecular-weight kininogen (HMWK) deficiency is a very rare hereditary disorder. We herein report a case of HMWK deficiency with splenic infarction. The HMWK activity of the proband was markedly decreased (0.9%). Direct sequencing of his HMWK gene showed a homozygous "TC" insertion at c523-524 in exon 4. This insertion led to an amino acid substitution, Ser175Ser, resulting in a frameshift mutation and a premature stop codon in amino acid 183. Furthermore, the HMWK activity was also reduced in the patient's three children, who exhibited the heterozygous "TC" insertion at c523-524 in exon 4. This is the first report of this gene alteration in a patient with HMWK deficiency.
Department of Medical Science Technology, School of Health Sciences at Fukuoka, International University of Health and Welfare, Japan.
Noriyasu
N
Fukushima
Hidekazu
H
Itamura
Hideo
H
Wada
Makoto
M
Ikejiri
Yuko
Y
Igarashi
Hiroya
H
Masaki
Masayuki
M
Sano
Yutaka
Y
Komiyama
Tatsuo
T
Ichinohe
Shinya
S
Kimura
D000368:Aged; D001778:Blood Coagulation Disorders / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000172:deficiency* / Q000235:genetics; D008297:Male; D010375:Pedigree; D013159:Splenic Infarction / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*
D019679:Kininogen, High-Molecular-Weight