Familial thoracic aortic aneurysms and dissections: genetic heterogeneity with a major locus mapping to 5q13-14.
نویسندگان
چکیده
BACKGROUND Aneurysms and dissections affecting the ascending aorta are associated primarily with degeneration of the aortic media, called medial necrosis. Families identified with dominant inheritance of thoracic aortic aneurysms and dissections (TAA/dissections) indicate that single gene mutations can cause medial necrosis in the absence of an associated syndrome. METHODS AND RESULTS Fifteen families were identified with multiple members with TAAs/dissections. DNA from affected members from 2 of the families was used for a genome-wide search for the location of the defective gene by use of random polymorphic markers. The data were analyzed by the affected-pedigree-member method of linkage analysis. This analysis revealed 3 chromosomal loci with multiple markers demonstrating evidence of linkage to the phenotype. Linkage analysis using further markers in these regions and DNA from 15 families confirmed linkage of some of the families to 5q13-14. Genetic heterogeneity for the condition was confirmed by a heterogeneity test. Data from 9 families with the highest conditional probability of being linked to 5q were used to calculate the pairwise and multipoint logarithm of the odds (LOD) scores, with a maximum LOD of 4.74, with no recombination being obtained for the marker D5S2029. In 6 families, the phenotype was not linked to the 5q locus. CONCLUSIONS A major locus for familial TAAs and dissections maps to 5q13-14, with the majority (9 of 15) of the families identified demonstrating evidence of linkage to this locus. The condition is genetically heterogeneous, with 6 families not demonstrating evidence of linkage to any loci previously associated with aneurysm formation.
منابع مشابه
Candidate locus analysis of familial ascending aortic aneurysms and dissections confirms the linkage to the chromosome 5q13-14 in Finnish families.
OBJECTIVE The purpose of the study was to carry out a candidate gene analysis in families with familial thoracic aortic aneurysms and dissections. METHODS The study material consisted of 11 Finnish families (with 115 members genotyped) who underwent echocardiographic examination for measurement of the aortic root diameter. Selected candidate genes included the loci for Marfan and Ehlers-Danlo...
متن کاملUnraveling the genetic predisposition for aortic aneurysms: is it time for tailored medicine?
A neurysms and dissections are the major pathologies affecting the thoracic aorta. Based on available data, up to 20% of individuals with thoracic aortic aneurysms (TAAs) may have a first-degree relative with aortic aneurysms or dissection, indicating a strong genetic predisposition.1 Within families, TAAs are inherited primarily in an autosomal dominant manner, with decreased penetrance and va...
متن کاملMapping a locus for familial thoracic aortic aneurysms and dissections (TAAD2) to 3p24-25.
BACKGROUND Familial thoracic aortic aneurysms and dissections (TAAD) occur as part of known syndromes such as Marfan syndrome but can also be inherited in families in an autosomal dominant manner as an isolated condition. Previous studies have mapped genes causing nonsyndromic familial TAAD to 5q13-15 (TAAD1) and 11q23.2-q24 (FAA1). Further genetic heterogeneity for the condition was evident by...
متن کاملFamilial thoracic aortic aneurysms and dissections: identification of a novel locus for stable aneurysms with a low risk for progression to aortic dissection.
BACKGROUND Thoracic aortic aneurysms leading to acute aortic dissections are the major diseases that affect the thoracic aorta. Approximately 20% of patients with thoracic aortic aneurysms and dissections (TAAD) have a family history of TAAD, and these patients present younger with more rapidly enlarging aneurysms than patients without a family history of aortic disease. METHODS AND RESULTS A...
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ورودعنوان ژورنال:
- Circulation
دوره 103 20 شماره
صفحات -
تاریخ انتشار 2001