A novel mutation of the fibrillin gene causing Ectopia lentis
- National Public Health Institute, Helsinki (Finland)
- St. George's Hospital Medical School, London (United Kingdom)
- Duncan Guthrie Institute, Glasgow, Scotland (United Kingdom)
Ectopia lentis (EL), a dominantly inherited connective tissue disorder, has been genetically linked to the fibrillin gene on chromosome 15 (FBN1) in earlier studies. Here, the authors report the first EL mutation in the FBN1 gene confirming that EL is caused by mutations of this gene. So far, several mutations in the FBN1 gene have been reported in patients with Marfan syndrome (MFS). EL and MFS are clinically related but distinct conditions with typical manifestations in the ocular and skeletal systems, the fundamental difference between them being the absence of cardiovascular involvement in EL. They report a point mutation, cosegregating with the disease in the described family, that displays EL over four generations. The mutation changes a conserved glutamic acid residue in an EGF-like motif, which is the major structural component of the fibrillin and is repeated throughout the polypeptide. In vitro mutagenetic studies have demonstrated the necessity of an analogous glutamic acid residue for calcium binding in an EGF-like repeat of human factor IX. This provides a possible explanation for the role of this mutation in the disease pathogenesis. 32 refs., 2 figs., 1 tab.
- OSTI ID:
- 6553750
- Journal Information:
- Genomics; (United States), Journal Name: Genomics; (United States) Journal Issue: 3 Vol. 19:3; ISSN GNMCEP; ISSN 0888-7543
- Country of Publication:
- United States
- Language:
- English
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