[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Thoracic aortic aneurysms and dissections can occur in families with autosomal dominant inheritance. Mutations in the fibrillin-1 gene on chromosome 15 cause Marfan syndrome (MFS), a known cause of familial aortic aneurysms and dissections. Affected individuals have phenotypic stigmata involving the skeletal, ophthalmologic and other systems. Mutations in the type III procollagen gene cause the vascular type of Ehlers-Danlos syndrome (EDS IV), which can include aneurysms that involve the aorta and other arteries, but account for a small minority of aortic aneurysms. Affected individuals have characteristic skin and joint findings. Families with no external phenotypic stigmata of connective tissue disorders have been reported as cases of Erdheim disease or annuloaortic ectasia. The causative gene(s) have not yet been identified.
Genetics in Medicine 01/2000; 2(1). DOI:10.1097/00125817-200001000-00083 · 7.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report on a family with severe X-linked mental retardation (XLMR) and progressive, severe central nervous system deterioration. Three of the five affected males died of secondary complications before the age of 10 years and none have survived past the age of 10. These complications included swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections. In addition, hypotonia and a mild myopathy were also present. All had a characteristic facies, including downslanting palpebral fissures, hypertelorism, and a short nose with a low nasal bridge. The two older boys showed cerebral atrophy by CT. No metabolic abnormalities were identified. Three obligate carriers had an IQ less than 80. The causal gene has been localized distal to DXS8103 in Xq28, a region spanning 5cM. No other XLMR disorder with these manifestations have been localized to this region and this appears to be a new disorder.
American Journal of Medical Genetics 08/1999; 85(3):243-8. · 3.23 Impact Factor