Autosomal dominant Marfan-like connective-tissue disorder with aortic dilation and skeletal anomalies not linked to the fibrillin genes

• Published in: American journal of human genetics 1993-07, Vol.53 (1), p.46-54
• Main Authors: BOILEAU, C, JONDEAU, G, BOURDARIAS, J.-P, JUNIEN, C, BABRON, M.-C, COULON, M, ALEXANDRE, J.-A, SAKAI, L, MELKI, J, DELORME, G, DUBOURG, O, BONAÏTI-PELLIE, C
• Format: Article
• Language: English
• Subjects: Adult; Aorta - abnormalities; Biological and medical sciences; Bone and Bones - abnormalities; chromosome 15; chromosome 5; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 5; Connective Tissue Diseases - genetics; Connective Tissue Diseases - pathology; Female; fibrillin; Fibrillins; genes; Genes, Dominant; Genetic Linkage; genetic markers; Humans; linkage analysis; Male; man; Marfan syndrome; Medical sciences; Microfilament Proteins - genetics; mutation; Original; Pedigree; Polymorphism, Genetic; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Syndrome
• ISSN: 0002-9297; 1537-6605

We describe a large family with a connective-tissue disorder that exhibits some of the skeletal and cardiovascular features seen in Marfan syndrome. However, none of the 19 affected individuals displayed ocular abnormalities and therefore did not comply with recognized criteria for this disease. These patients could alternatively be diagnosed as MASS (mitral valve, aorta, skeleton, and skin) phenotype patients or represent a distinct clinical entity, i.e., a new autosomal dominant connective-tissue disorder. The fibrillin genes located on chromosomes 15 and 5 are clearly involved in the classic form of Marfan syndrome and a clinically related disorder (congenital contractural arachnodactyly), respectively. To test whether one of these genes was also implicated in this French family, we performed genetic analyses. Blood samples were obtained for 56 family members, and four polymorphic fibrillin gene markers, located on chromosomes 15 (Fib15) and 5 (Fib5), respectively, were tested. Linkage between the disease allele and the markers of these two genes was excluded with lod scores of -11.39 (for Fib15) and -13.34 (for Fib5), at theta = .001, indicating that the mutation is at a different locus. This phenotype thus represents a new connective-tissue disorder, overlapping but different from classic Marfan syndrome.