Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Mutations in the gene encoding extracellular glycoprotein fibrillin-1 (FBN1) cause Marfan syndrome (MFS) and other related connective tissue disorders. In this study, eight mutations have been detected in MFS patients by heteroduplex analysis. These comprise two missense mutations, C1835Y and C2258Y in calcium-binding epidermal growth factor-like domains, two nonsense mutations, R1541X and R2394X in transforming growth factor beta1-binding protein-like domains, one splice site mutation, which has been detected previously, and three small insertions or deletions resulting in a frameshift. Fibroblast cells have been established from seven of the MFS patients and the biochemical effects of the mutations on fibrillin-1 synthesis and secretion assessed by pulse-chase analysis. Each cysteine mutation resulted in the delayed secretion of fibrillin-1 and both nonsense and frameshift mutations caused reduced levels of synthesis and/or deposition of fibrillin-1. Indirect immunofluorescence and rotary shadowing electron microscopy analysis of fibrillin microfibrils revealed no major differences between normal and patient samples. We discuss the relative merits of the biochemical techniques used in this study.

Original publication

DOI

10.1007/s004390051150

Type

Journal article

Journal

Human genetics

Publication Date

12/1999

Volume

105

Pages

587 - 597

Addresses

Wellcome Trust Centre for Human Genetics, University of Oxford, UK.

Keywords

Cells, Cultured, Fibroblasts, Humans, Marfan Syndrome, Microfilament Proteins, Extracellular Matrix Proteins, Microscopy, Electron, Fluorescent Antibody Technique, Indirect, Polymerase Chain Reaction, DNA Mutational Analysis, Frameshift Mutation, Point Mutation, Adult, Child, Preschool, Female, Male, Fibrillin-1, Fibrillins