N Engl J Med 2011; 364:43-50January 6, 2011
Gigantism results when a growth hormone–secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783,1-3 he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon–interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.
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From the Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London (H.S.C., G.M.B., S.A.A., A.B.G., M.K.); the Institute of Genetics (D.J.B.) and the Research Department of Genetics, Evolution and Environment (M.G.T.), University College London; North East Thames Regional Genetics Service, Great Ormond Street Hospital (A.V.K.); and the Department of Mineralogy, Natural History Museum (R.L.A.) — all in London; the Department of Molecular Genetics, Royal Devon and Exeter Foundation Trust (K.S., S.E.), and Peninsula Medical School, University of Exeter (S.E.) — both in Exeter; Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital (A.B.A.), and the Department of Medical Genetics, Belfast HSC Trust (P.J.M.) — both in Belfast, Northern Ireland; the School of Biomedical Science, University of Ulster, Coleraine, Northern Ireland (P.J.M.); the Department of Endocrinology, University Hospitals of Leicester, Leicester (T.A.H., M.J.L.); and the Department of Endocrinology, St James's University Hospital, Leeds (S.M.O.) — all in the United Kingdom; the Institute of Anthropology, Johannes Gutenberg University, Mainz, Germany (M.U., J.B.); the Department of Evolutionary Biology, Evolutionary Biology Center, Uppsala University, Uppsala, Sweden (M.G.T.).