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(Circulation. 2003;107:3184.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Mapping a Locus for Familial Thoracic Aortic Aneurysms and Dissections (TAAD2) to 3p24–25

Sumera N. Hasham, PhD; Marcia C. Willing, MD, PhD; Dong-chuan Guo, PhD; Ann Muilenburg, MA; Rumin He, MD; Van T. Tran, MS; Steven E. Scherer, PhD; Sanjay S. Shete, PhD; Dianna M. Milewicz, MD, PhD

From the Department of Internal Medicine, University of Texas Medical School at Houston (S.N.H., D.-c.G., R.H., V.T.T., D.M.); the Department of Pediatrics, University of Iowa, Iowa City (M.C.W., A.M.); Human Genome Sequencing Center, Baylor College of Medicine, Houston, Tex (S.E.S.); and the Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Tex (S.S.S.).

Correspondence to Dianna M. Milewicz, MD, PhD, 6431 Fannin, MSB 1.614, Houston, TX 77030. E-mail Dianna.M.Milewicz{at}uth.tmc.edu

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 the presence of TAAD in some families not linked to these known loci.

Methods and Results— A 4-generation family with dominant mode of inheritance of TAAD was studied. Affected status was determined by dilation of the ascending aorta, surgical repair of an aneurysm or dissection, or death as the result of aortic dissection. None of the family members evaluated met the diagnostic criteria for Marfan syndrome. After exclusion of known loci for familial TAAD, a genome-wide scan was carried out to map the defective gene causing the disease in the family. A locus was mapped to a 25-cM region on 3p24–25 with a maximum multipoint logarithm of the odds score of 4.28.

Conclusions— A third locus for nonsyndromic TAAD was mapped to 3p24–25 and termed the TAAD2 locus. This locus overlaps a previously mapped second locus for Marfan syndrome, termed the MFS2 locus. Future characterization of the TAAD2 gene will determine if TAAD2 is allelic to MFS2. In addition, identification of the TAAD2 gene will improve the presymptomatic diagnosis of individuals with this life-threatening genetic syndrome and provide information concerning the pathogenesis of the disease.

Key Words: aorta • aneurysm • genetics • mapping

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