Section 9
Chapter 8,060

A novel de novo mutation in exon 14 of the fibrillin-1 gene associated with delayed secretion of fibrillin in a patient with a mild Marfan phenotype

Booms, P.; Withers, A.P.; Boxer, M.; Kaufmann, U.C.; Hagemeier, C.; Vetter, U.; Robinson, P.N.

Human Genetics 100(2): 195-200


ISSN/ISBN: 0340-6717
PMID: 9254848
DOI: 10.1007/s004390050489
Accession: 008059665

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The Marfan syndrome, an autosomal dominant heritable disorder of connective tissue, is caused by mutations in the gene for fibrillin-1, FBN1. A novel FBN1 mutation was identified using temperature-gradient gel electrophoresis of a reverse-transcribed polymerase chain reaction product spanning exons 14 to 16. The mutation, G1760A, is predicted to result in the amino acid substitution C587Y and thus to disrupt one of the disulfide bonds of the calcium-binding epidermal growth factor-like module encoded by exon 14. C587Y was found to be a de novo mutation in a relatively mildly affected 15-year-old girl whose clinical phenotype was characterized mainly by ectopia lentis and thoracic scoliosis. Metabolic labeling of cultured dermal fibroblasts from the affected patient demonstrated delayed secretion of fibrillin with normal synthesis and no decrease in incorporation into the extracellular matrix compartment. Fibrillin immunostaining of confluent dermal fibroblast cultures revealed no visible difference between the patient's cells and control cells. Characterization of many different FBN1 mutations from different regions of the gene may provide a better understanding of clinical and biochemical genotype-phenotype relationships.

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