Variable phenotype of Marfan syndrome in two large Australian pedigrees, one of Australian aboriginal origin
- Univ. of Queensland (Australia); and others
Marfan syndrome may affect the cardiovascular, ocular and skeletal systems. The gene for this autosomal dominant disease maps to chromosome 15 and codes for the extracellular matrix protein fibrillin. Phenotypic expression is very variable both within and between families, possibly due to the influence of other, unlinked, genetic factors interacting with the fibrillin gene. We report two Australian families which demonstrate the extent of inter- and intra-family phenotypic variability. Eye, cardiac and skeletal assessments were made independently. In the first family, 8 of 12 siblings and 11 of 19 of their children had ectopia lentis with or without other ocular findings. There were few cardiac signs. One child had mitral valve prolapse. He and three other children had mild dilatation of the aorta. Skeletal abnormalities were also found (3 adults and 7 children). Chest wall asymmetry was the most common skeletal finding. This family has less cardiac and skeletal involvement than is usual in Marfan syndrome, although the disease maps to chromosome 15 in the region of the fibrillin gene (LOD=4.8 at {theta}=0 with respect to CYP19). The second family is partly of Australian aboriginal origin. The disease has been traced through 5 generations. To date we have examined 37 of 84 living members. Twenty-three in 3 generations are affected. Five adults and 4 children have moderate to severe aortic dilatation and there has been at least one death due to aortic dissection. However, two adolescents with subluxed lenses and marked skeletal abnormalities have normal aortic diameters, two children have aortic dilatation without other signs and two children have only subluxed lenses. This family shows the range of phenotypic variation which can arise from mutation in the fibrillin gene, which may be influenced by the admixture of Australian aboriginal genes. These two families provide an invaluable resource for studying genetic interactions in this disease.
- OSTI ID:
- 133638
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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