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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-1003 Copyright © 2008 by The Endocrine Society
Large Genomic Deletions in AIP in Pituitary Adenoma PredispositionMarianthi Georgitsi, Elina Heliövaara, Ralf Paschke, Ajith V. K. Kumar, Marc Tischkowitz, Outi Vierimaa, Pasi Salmela, Timo Sane, Ernesto De Menis, Salvatore Cannavò, Sadi Gündogdu, Anneke Lucassen, Louise Izatt, Simon Aylwin, Gul Bano, Shirley Hodgson, Christian A. Koch, Auli Karhu and Lauri A. AaltonenDepartment of Medical Genetics (M.G., E.H., A.K., L.A.A.), 00014 University of Helsinki, Helsinki, Finland; Medical Department III (R.P.), Leipzig University, 04103 Leipzig, Germany; Clinical Genetics (A.V.K.K.), Great Ormond Street National Health Service Trust, London WC1N 3JH, United Kingdom; Departments of Human Genetics, Oncology, and Medicine (M.T.), McGill University, Sir Mortimer B. Davis Jewish General Hospital, H3T 1E2 Montreal, Quebec, Canada; Departments of Clinical Genetics (O.V.) and Internal Medicine (P.S.), Oulu University Hospital, 90029 Oulu, Finland; Department of Endocrinology (T.S.), Helsinki University Central Hospital, 00029 Helsinki, Finland; Department of Internal Medicine (E.D.M.), General Hospital, 31044 Montebelluna, Italy; Department of Medicine and Pharmacology (S.C.), Section of Endocrinology, University of Messina, 98125 Messina, Italy; Division of Endocrinology-Metabolism and Diabetes (S.G.), Cerrahpaçsa Medical Faculty, University of Istanbul, 34303 Istanbul, Turkey; Wessex Clinical Genetics Service (A.L.), Princess Anne Hospital, SO16 5YA Southampton, United Kingdom; Department of Clinical Genetics (L.I.), New Guy’s House, Guy’s Hospital, London SE1 9RT, United Kingdom; Department of Medicine (S.A.), King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom; Department of Endocrinology and Diabetes (G.B.), Thomas Addison Unit, London SW17 0QT, United Kingdom; Department of Clinical Genetics (S.H.), St. Georges, University of London, London SW17 ORE, United Kingdom; and Division of Endocrinology (C.A.K.), University of Mississippi Medical Center, Jackson, Mississippi 39216 Address all correspondence and requests for reprints to: Professor Lauri A. Aaltonen, Department of Medical Genetics, Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), University of Helsinki, 00014 Helsinki, Finland. E-mail: lauri.aaltonen{at}helsinki.fi. Context: Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings. Objective: Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP. Design: Here, we applied the multiplex ligation-dependent probe amplification assay to examine whether large genomic AIP or MEN1 alterations account for a subset of PAP cases. Patients: The study was performed on familial and sporadic pituitary adenoma cases of European origin, which had previously tested negative for germline AIP and MEN1 mutations by sequencing. Results: Two of 21 pituitary adenoma families (9.5%) were found to harbor an AIP deletion. No copy number changes were detected among 67 sporadic pituitary adenoma patients. No MEN1 deletions were found. Conclusions: The present study shows that large genomic AIP deletions account for a subset of PAP. Therefore, in suspected PAP cases undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe amplification could be considered if direct sequencing does not identify a mutation. This article has been cited by other articles:
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