Molecular analysis of eight mutations in FBN1.
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
1999
|
| _version_ | 1797076141146636288 |
|---|---|
| author | Halliday, D Hutchinson, S Kettle, S Firth, H Wordsworth, P Handford, P |
| author_facet | Halliday, D Hutchinson, S Kettle, S Firth, H Wordsworth, P Handford, P |
| author_sort | Halliday, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:59:57Z |
| format | Journal article |
| id | oxford-uuid:75973183-1c56-47f3-8fd4-3cf5a97adaf3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:59:57Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:75973183-1c56-47f3-8fd4-3cf5a97adaf32022-03-26T20:10:23ZMolecular analysis of eight mutations in FBN1.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:75973183-1c56-47f3-8fd4-3cf5a97adaf3EnglishSymplectic Elements at Oxford1999Halliday, DHutchinson, SKettle, SFirth, HWordsworth, PHandford, PMutations 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. |
| spellingShingle | Halliday, D Hutchinson, S Kettle, S Firth, H Wordsworth, P Handford, P Molecular analysis of eight mutations in FBN1. |
| title | Molecular analysis of eight mutations in FBN1. |
| title_full | Molecular analysis of eight mutations in FBN1. |
| title_fullStr | Molecular analysis of eight mutations in FBN1. |
| title_full_unstemmed | Molecular analysis of eight mutations in FBN1. |
| title_short | Molecular analysis of eight mutations in FBN1. |
| title_sort | molecular analysis of eight mutations in fbn1 |
| work_keys_str_mv | AT hallidayd molecularanalysisofeightmutationsinfbn1 AT hutchinsons molecularanalysisofeightmutationsinfbn1 AT kettles molecularanalysisofeightmutationsinfbn1 AT firthh molecularanalysisofeightmutationsinfbn1 AT wordsworthp molecularanalysisofeightmutationsinfbn1 AT handfordp molecularanalysisofeightmutationsinfbn1 |