The Familial Intracranial Aneurysm (FIA) study protocol
<p>Abstract</p> <p>Background</p> <p>Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms (IAs) occurs in about 20,000 people per year in the U.S. annually and nearly half of the affected persons are dead within the first 30 days. Survivors of ruptured I...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2005-04-01
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| Series: | BMC Medical Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2350/6/17 |
| _version_ | 1818559907083845632 |
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| author | Meissner Irene Pankratz Nathan Huston John Foroud Tatiana Sauerbeck Laura R Broderick Joseph P Brown Robert D |
| author_facet | Meissner Irene Pankratz Nathan Huston John Foroud Tatiana Sauerbeck Laura R Broderick Joseph P Brown Robert D |
| author_sort | Meissner Irene |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms (IAs) occurs in about 20,000 people per year in the U.S. annually and nearly half of the affected persons are dead within the first 30 days. Survivors of ruptured IAs are often left with substantial disability. Thus, primary prevention of aneurysm formation and rupture is of paramount importance. Prior studies indicate that genetic factors are important in the formation and rupture of IAs. The long-term goal of the Familial Intracranial Aneurysm (FIA) Study is to identify genes that underlie the development and rupture of intracranial aneurysms (IA).</p> <p>Methods/Design</p> <p>The FIA Study includes 26 clinical centers which have extensive experience in the clinical management and imaging of intracerebral aneurysms. 475 families with affected sib pairs or with multiple affected relatives will be enrolled through retrospective and prospective screening of potential subjects with an IA. After giving informed consent, the proband or their spokesperson invites other family members to participate. Each participant is interviewed using a standardized questionnaire which covers medical history, social history and demographic information. In addition blood is drawn from each participant for DNA isolation and immortalization of lymphocytes. High- risk family members without a previously diagnosed IA undergo magnetic resonance angiography (MRA) to identify asymptomatic unruptured aneurysms. A 10 cM genome screen will be performed to identify FIA susceptibility loci. Due to the significant mortality of affected individuals, novel approaches are employed to reconstruct the genotype of critical deceased individuals. These include the intensive recruitment of the spouse and children of deceased, affected individuals.</p> <p>Discussion</p> <p>A successful, adequately-powered genetic linkage study of IA is challenging given the very high, early mortality of ruptured IA. Design features in the FIA Study that address this challenge include recruitment at a large number of highly active clinical centers, comprehensive screening and recruitment techniques, non-invasive vascular imaging of high-risk subjects, genome reconstruction of dead affected individuals using marker data from closely related family members, and inclusion of environmental covariates in the statistical analysis.</p> |
| first_indexed | 2024-12-14T00:31:37Z |
| format | Article |
| id | doaj.art-e37626b397704af589d068bc63877cc4 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-14T00:31:37Z |
| publishDate | 2005-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-e37626b397704af589d068bc63877cc42022-12-21T23:24:50ZengBMCBMC Medical Genetics1471-23502005-04-01611710.1186/1471-2350-6-17The Familial Intracranial Aneurysm (FIA) study protocolMeissner IrenePankratz NathanHuston JohnForoud TatianaSauerbeck Laura RBroderick Joseph PBrown Robert D<p>Abstract</p> <p>Background</p> <p>Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms (IAs) occurs in about 20,000 people per year in the U.S. annually and nearly half of the affected persons are dead within the first 30 days. Survivors of ruptured IAs are often left with substantial disability. Thus, primary prevention of aneurysm formation and rupture is of paramount importance. Prior studies indicate that genetic factors are important in the formation and rupture of IAs. The long-term goal of the Familial Intracranial Aneurysm (FIA) Study is to identify genes that underlie the development and rupture of intracranial aneurysms (IA).</p> <p>Methods/Design</p> <p>The FIA Study includes 26 clinical centers which have extensive experience in the clinical management and imaging of intracerebral aneurysms. 475 families with affected sib pairs or with multiple affected relatives will be enrolled through retrospective and prospective screening of potential subjects with an IA. After giving informed consent, the proband or their spokesperson invites other family members to participate. Each participant is interviewed using a standardized questionnaire which covers medical history, social history and demographic information. In addition blood is drawn from each participant for DNA isolation and immortalization of lymphocytes. High- risk family members without a previously diagnosed IA undergo magnetic resonance angiography (MRA) to identify asymptomatic unruptured aneurysms. A 10 cM genome screen will be performed to identify FIA susceptibility loci. Due to the significant mortality of affected individuals, novel approaches are employed to reconstruct the genotype of critical deceased individuals. These include the intensive recruitment of the spouse and children of deceased, affected individuals.</p> <p>Discussion</p> <p>A successful, adequately-powered genetic linkage study of IA is challenging given the very high, early mortality of ruptured IA. Design features in the FIA Study that address this challenge include recruitment at a large number of highly active clinical centers, comprehensive screening and recruitment techniques, non-invasive vascular imaging of high-risk subjects, genome reconstruction of dead affected individuals using marker data from closely related family members, and inclusion of environmental covariates in the statistical analysis.</p>http://www.biomedcentral.com/1471-2350/6/17 |
| spellingShingle | Meissner Irene Pankratz Nathan Huston John Foroud Tatiana Sauerbeck Laura R Broderick Joseph P Brown Robert D The Familial Intracranial Aneurysm (FIA) study protocol BMC Medical Genetics |
| title | The Familial Intracranial Aneurysm (FIA) study protocol |
| title_full | The Familial Intracranial Aneurysm (FIA) study protocol |
| title_fullStr | The Familial Intracranial Aneurysm (FIA) study protocol |
| title_full_unstemmed | The Familial Intracranial Aneurysm (FIA) study protocol |
| title_short | The Familial Intracranial Aneurysm (FIA) study protocol |
| title_sort | familial intracranial aneurysm fia study protocol |
| url | http://www.biomedcentral.com/1471-2350/6/17 |
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