Related Experiment Videos
[Cerebrovascular accidents with familial antithrombin III deficiency--gene analysis study]
Shinya Tsukahara1, Takahiro Iizuka, Norihiro Suzuki
1Department of Internal Medicine (Neurology), School of Medicine, Kitasato University.
Insights
Familial antithrombin III (AT III) type I deficiency can cause cerebral infarction. A novel gene mutation was identified in a Japanese family with this rare condition, leading to stroke in multiple members.
Area of Science:
- Genetics
- Neurology
- Hematology
Background:
- Cerebral infarction, or stroke, can be linked to inherited thrombotic disorders.
- Familial antithrombin III (AT III) type I deficiency is a rare genetic condition predisposing individuals to blood clots.
Observation:
- Two cases of cerebral infarction (deep cerebral vein thrombosis and top of the basilar syndrome) were observed in a Japanese family.
- Cerebral infarction affected multiple members within the same family pedigree.
- Eighteen family members were tested, revealing that 6 individuals (33%) had AT III type I deficiency.
Findings:
- Genetic analysis identified a novel 4-base CTTT frame shift insertion mutation in the AT III gene (exon 2) in a patient with cerebral infarction.
- This specific type of AT III deficiency mutation is exceptionally rare, with only twelve previously reported pedigrees worldwide.
- This represents the first documented case of AT III type I deficiency caused by a frame shift insertion mutation in Japan.
Implications:
- Highlights the importance of genetic screening for antithrombin III deficiency in families with recurrent cerebral infarction.
- Identifies a novel mutation contributing to thrombophilia, expanding the known genetic landscape of AT III deficiency.
- Emphasizes the clinical significance of rare genetic thrombotic disorders in stroke etiology, particularly in specific geographic populations.
Abstract:
We report two cases of the cerebral infarction with familial antithrombin III type I deficiency. Case 1 is a 47-year-old woman presenting deep cerebral vein thrombosis. Case 2 is a 20-year-old man presenting the top of the basilar syndrome. Beside them, substantial number of members had cerebral infarction in this pedigree. We measured AT III activity and quantity for 18 persons in this pedigree. As a consequence, 6 of 18 persons in this pedigree had AT III type I deficiency. Analysis of PCR products of AT III gene derived from the case 1's leukocyte DNA revealed a novel frame shift insertion was demonstrated as mutant alleles with 4-base CTTT in nt 2,420 or nt 2,424 in exon 2 domain on the AT III gene. AT III type I deficiency caused by frame shift insertion has been reported only twelve pedigrees. This is the first case report of AT III type I deficiency caused by frame shift insertion in Japan.