a spectrum of severe familial liver disorders associate with telomerase mutations光谱严重的家族性肝疾病与端粒酶突变.pdfVIP

A Spectrum of Severe Familial Liver Disorders Associate with Telomerase Mutations 1. 1. 2 3 1 Rodrigo T. Calado *, Joshua A. Regal , David E. Kleiner , David S. Schrump , Nathan R. Peterson , 5 4 6 1 Veronica Pons , Stephen J. Chanock , Peter M. Lansdorp , Neal S. Young 1 Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 3 Thoracic Oncology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 4 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 5 Hematology Department, Hospital Vall d’Hebron, Barcelona, Spain, 6 British Columbia Cancer Agency and Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada Abstract Background: Telomerase is an enzyme specialized in maintaining telomere lengths in highly proliferative cells. Loss-of- function mutations cause critical telomere shortening and are associated with the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia and with idiopathic pulmonary fibrosis. Here, we sought to determine the spectrum of clinical manifestations associated with telomerase loss-of-function mutations. Methodology/Principal Findings: Sixty-nine individuals from five unrelated familie