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A molecular genetic study of intracerebral hemorrhage
C Graffagnino1, M H Herbstreith, A D Roses
1Department of Medicine, Duke University Medical Center, Durham, NC.
Insights
Researchers investigated genetic mutations in amyloid precursor protein and cystatin C genes in patients with sporadic intracerebral hemorrhage (ICH). No mutations linked to familial ICH were identified in this patient group.
Area of Science:
- Neurology
- Genetics
- Cerebrovascular Disease
Background:
- Inherited intracerebral hemorrhage (ICH) is linked to amyloid angiopathy.
- Mutations in amyloid precursor protein (APP) or cystatin C genes cause familial ICH.
- Sporadic ICH is a common form of stroke with various underlying causes.
Purpose of the Study:
- To investigate mutations in APP and cystatin C genes in patients with sporadic ICH.
- To determine if genetic factors known to cause familial ICH are present in sporadic cases.
Main Methods:
- Consecutive patients with ICH were recruited from neurology and neurosurgery services.
- Polymerase chain reaction (PCR) was used to amplify specific gene regions (APP exons 16-17, cystatin C exon 2).
- DNA sequencing was performed on amplified products to identify mutations.
Main Results:
- A total of 48 patients (26 men, 22 women) with ICH were studied.
- ICH locations varied, including deep, lobar, cerebellar, and brain stem.
- A significant proportion (63%) had a family history of stroke, with 15% having a family history of ICH.
Conclusions:
- No mutations previously associated with familial forms of ICH were detected in patients with sporadic ICH.
- The genetic basis for sporadic ICH likely differs from the identified familial forms.
- Further research is needed to elucidate the genetic underpinnings of sporadic ICH.
Background:
Two forms of inherited intracerebral hemorrhage (ICH) are associated with an amyloid angiopathy caused by mutations in the genes for the amyloid precursor protein or cystatin C. The purpose of this study was to determine whether patients with sporadic ICH have mutations in the amyloid precursor protein or cystatin C genes.
Methods:
Consecutive patients with ICH admitted to the neurology or neurosurgery services at Duke University Hospital, Durham, NC, were studied. Using the polymerase chain reaction, we amplified exons 16 and 17 of the amyloid precursor protein and exon 2 of cystatin C and sequenced the products. Twenty-six men and 22 women were studied. The ICH location was deep in 29 patients, lobar in 16, cerebellar in two, and brain stem in one. There were 30 patients (63%) with a positive family history of stroke; seven of them (15%) had a family history of ICH.
Conclusions:
Mutations previously reported to cause familial forms of ICH were not found in this group of patients.