Paleogenetic study of ancient DNA suggestive of X-linked acrogigantism

    1. Adrian F Daly1
    1. 1Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium
    2. 2School of Archaeology and Earth Institute, University College Dublin, Belfield, Dublin, Ireland
    3. 3Department of Life Sciences, Centro de Investigação em Antropologia e Saúde, University of Coimbra, Coimbra, Portugal
    4. 4Assistance Publique Hôpitaux de Marseille (AP-HM) Hôpital Nord, Service de Transfert d’Oncologie Biologique, and Laboratoire de Biologie Médicale, and Aix-Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France
    5. 5Department of Legal Medicine, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium
    6. 6Department of Pathology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium
    7. 7Office of the Conservator, Muséum régionale des Sciences naturelles, Mons, Belgium
    1. Correspondence should be addressed to A Beckers; email: albert.beckers{at}chu.ulg.ac.be

    Dear Editor,

    Pituitary gigantism is caused by chronic growth hormone (GH) hypersecretion by a pituitary lesion before epiphyseal fusion. Genetic causes have been identified in nearly 50% of patients with pituitary gigantism, with germline mutations in the AIP gene being the most frequent cause (Rostomyan et al. 2015). Recently, a new form of pituitary gigantism, X-linked acrogigantism (X-LAG), was described (Trivellin et al. 2014). X-LAG is due to chromosome Xq26.3 duplication, and GPR101 is the disease-associated gene (Trivellin et al. 2014, Iacovazzo et al. 2016). X-LAG is characterized by mixed GH/prolactin-secreting pituitary macroadenomas and/or hyperplasia in early childhood (Beckers et al. 2015). X-LAG typically occurs sporadically in females, but somatic mosaicism also occurs in males; familial mother-to-son transmission of the Xq26.3 duplication has been reported in three familial isolated pituitary adenoma families (Trivellin et al. 2014, Daly et al. 2016, Gordon et al. 2016, Iacovazzo et al. 2016). The clinical presentation of X-LAG syndrome differs from other genetic forms of pituitary gigantism (Rostomyan et al. 2015), and many well-known historical cases of gigantism share the clinical characteristics of X-LAG syndrome (Beckers et al. 2015, Rostomyan et al. 2015). If untreated during childhood, X-LAG leads to established extreme gigantism (>1.9 m) before puberty (Daly et al. 2016).

    We studied a historical case of severe acrogigantism. The subject, J.K., was born in 1872 in Reutlingen, in what is now Baden-Württemberg, Germany. His parents and brother were of normal size. It was reported by his doctor that J.K. had always been ‘very large’ and he was reputed to have a huge appetite; he measured 1.94 m at the age of 14 and never stopped growing thereafter (Launois & Roy 1904). In contemporary Württemberg, the average adult male height was only 164 cm. By the 1890s he was exhibiting himself as Giant Constantine/Le …

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