title: AIP mutation in pituitary adenomas in the 18th century and today.
abstract: 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, 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.
authors.affiliation: Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Harvinder S
authors.initials: HS
authors.lastname: Chahal
authors.forename: Karen
authors.initials: K
authors.lastname: Stals
authors.forename: Martina
authors.initials: M
authors.lastname: Unterländer
authors.forename: David J
authors.initials: DJ
authors.lastname: Balding
authors.forename: Mark G
authors.initials: MG
authors.lastname: Thomas
authors.forename: Ajith V
authors.initials: AV
authors.lastname: Kumar
authors.forename: G Michael
authors.initials: GM
authors.lastname: Besser
authors.forename: A Brew
authors.initials: AB
authors.lastname: Atkinson
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Morrison
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Howlett
authors.forename: Miles J
authors.initials: MJ
authors.lastname: Levy
authors.forename: Steve M
authors.initials: SM
authors.lastname: Orme
authors.forename: Scott A
authors.initials: SA
authors.lastname: Akker
authors.forename: Richard L
authors.initials: RL
authors.lastname: Abel
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.forename: Joachim
authors.initials: J
authors.lastname: Burger
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
mesh_terms: D000172:Acromegaly / Q000235:genetics* / Q000266:history; D000236:Adenoma / Q000235:genetics* / Q000266:history; D005877:Gigantism / Q000235:genetics* / Q000266:history; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics* / Q000266:history; D006239:Haplotypes; D006579:Heterozygote; D049671:History, 18th Century; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D010911:Pituitary Neoplasms / Q000235:genetics*; D015175:Prolactinoma / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein