A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1.
OBJECTIVE: To investigate a family with an unusual combination of multiple endocrine neoplasia (MEN1) and the McCune-Albright syndrome for MEN1 mutations and activating GNAS1 mutations at codons Arg201 and Gln227. METHODS: DNA sequences analyses were performed of the MEN1 gene and codons Arg201 and...
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| Formaat: | Journal article |
| Taal: | English |
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2007
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| _version_ | 1826291373445218304 |
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| author | Lemos, M Harding, B Shalet, S Thakker, R |
| author_facet | Lemos, M Harding, B Shalet, S Thakker, R |
| author_sort | Lemos, M |
| collection | OXFORD |
| description | OBJECTIVE: To investigate a family with an unusual combination of multiple endocrine neoplasia (MEN1) and the McCune-Albright syndrome for MEN1 mutations and activating GNAS1 mutations at codons Arg201 and Gln227. METHODS: DNA sequences analyses were performed of the MEN1 gene and codons Arg201 and Gln227 of the GNAS1 gene, using leucocyte and endocrine tissue DNA. RESULTS: A c-->g transversion at position -9 bp in intron 9 of the MEN1 gene was identified. This resulted in the generation of a BmrI restriction endonuclease site, and its presence and segregation with MEN1 in the family was demonstrated by restriction endonuclease analysis. The c-->g transversion was shown to result in the generation of a novel acceptor splice site (ccag) using reverse transcriptase-polymerase chain reaction (RT-PCR) and ribonucleic acid (RNA) obtained from Epstein-Barr virus (EBV)-transformed lymphoblasts. Utilization of this splice site resulted in an abnormal messenger RNA (mRNA) transcript that contained an additional eight bases. This predicted a frameshift that would result in nine missense amino acids followed by a premature termination signal. GNAS1 mutations were not detected in the patient with McCune-Albright syndrome. CONCLUSIONS: The occurrence of MEN1 and the McCune-Albright syndrome in this family are coincidental findings and not due to a common genetic aetiology. However, our results have identified a novel MEN1 mutation that occurs in intron 9 and generates a novel acceptor splice site. Such splicing-affecting genomic variants (SpaGVs) are increasingly being recognized as a cause of human disease, and are likely to be of significance in the 10% of MEN1 patients who do not have coding region mutations. |
| first_indexed | 2024-03-07T02:58:25Z |
| format | Journal article |
| id | oxford-uuid:b01cf0d2-a370-451b-ae09-91e09393e74b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:58:25Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:b01cf0d2-a370-451b-ae09-91e09393e74b2022-03-27T03:54:06ZA novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b01cf0d2-a370-451b-ae09-91e09393e74bEnglishSymplectic Elements at Oxford2007Lemos, MHarding, BShalet, SThakker, ROBJECTIVE: To investigate a family with an unusual combination of multiple endocrine neoplasia (MEN1) and the McCune-Albright syndrome for MEN1 mutations and activating GNAS1 mutations at codons Arg201 and Gln227. METHODS: DNA sequences analyses were performed of the MEN1 gene and codons Arg201 and Gln227 of the GNAS1 gene, using leucocyte and endocrine tissue DNA. RESULTS: A c-->g transversion at position -9 bp in intron 9 of the MEN1 gene was identified. This resulted in the generation of a BmrI restriction endonuclease site, and its presence and segregation with MEN1 in the family was demonstrated by restriction endonuclease analysis. The c-->g transversion was shown to result in the generation of a novel acceptor splice site (ccag) using reverse transcriptase-polymerase chain reaction (RT-PCR) and ribonucleic acid (RNA) obtained from Epstein-Barr virus (EBV)-transformed lymphoblasts. Utilization of this splice site resulted in an abnormal messenger RNA (mRNA) transcript that contained an additional eight bases. This predicted a frameshift that would result in nine missense amino acids followed by a premature termination signal. GNAS1 mutations were not detected in the patient with McCune-Albright syndrome. CONCLUSIONS: The occurrence of MEN1 and the McCune-Albright syndrome in this family are coincidental findings and not due to a common genetic aetiology. However, our results have identified a novel MEN1 mutation that occurs in intron 9 and generates a novel acceptor splice site. Such splicing-affecting genomic variants (SpaGVs) are increasingly being recognized as a cause of human disease, and are likely to be of significance in the 10% of MEN1 patients who do not have coding region mutations. |
| spellingShingle | Lemos, M Harding, B Shalet, S Thakker, R A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1. |
| title | A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1. |
| title_full | A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1. |
| title_fullStr | A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1. |
| title_full_unstemmed | A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1. |
| title_short | A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1. |
| title_sort | novel men1 intronic mutation associated with multiple endocrine neoplasia type 1 |
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