A S von Krogh1,2, P Quist-Paulsen1,2, A Waage1,2, Ø O Langseth1, K Thorstensen3, R Brudevold4, G E Tjønnfjord5,6, C R Largiadèr7, B Lämmle8,9, J A Kremer Hovinga8,10. 1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, St Olavs Hospital Trondheim University Hospital, Trondheim, Norway. 2. Department of Haematology, St Olavs Hospital Trondheim University Hospital, Trondheim, Norway. 3. Department of Clinical Chemistry, St Olavs Hospital Trondheim University Hospital, Trondheim, Norway. 4. Department of Haematology, Møre and Romsdal Hospital Trust, Ålesund, Norway. 5. Department of Haematology, Oslo University Hospital, Oslo, Norway. 6. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 7. Department of Clinical Chemistry, Bern University Hospital and University of Bern, Inselspital, Bern, Switzerland. 8. Department of Haematology and Central Haematology Laboratory, Bern University Hospital and University of Bern, Inselspital, Bern, Switzerland. 9. Center for Thrombosis and Hemostasis (CTH), University Medical Center, Mainz, Germany. 10. Department of Clinical Research, University of Bern, Bern, Switzerland.
Abstract
UNLABELLED: Essentials The population prevalence of hereditary thrombotic thrombocytopenic purpura (TTP) is unknown. We studied the prevalence of hereditary TTP and population frequencies of two ADAMTS-13 mutations. A high frequency of hereditary TTP related to ADAMTS-13 mutation c.4143_4144dupA was found. Vicinity of ABO blood group and ADAMTS-13 loci may facilitate screening of ADAMTS-13 mutations. SUMMARY: Background Hereditary thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS-13 mutations is a rare, but serious condition. The prevalence is unknown, but it seems to be high in Norway. Objectives To identify all patients with hereditary TTP in central Norway and to investigate the prevalence of hereditary TTP and the population frequencies of two common ADAMTS-13 mutations. Patients/Methods Patients were identified in a cross-sectional study within the Central Norway Health Region by means of three different search strategies. Frequencies of ADAMTS-13 mutations, c.4143_4144dupA and c.3178 C>T (p.R1060W), were investigated in a population-based cohort (500 alleles) and in healthy blood donors (2104 alleles) by taking advantage of the close neighborhood of the ADAMTS-13 and ABO blood group gene loci. The observed prevalence of hereditary TTP was compared with the rates of ADAMTS-13 mutation carriers in different geographical regions. Results We identified 11 families with hereditary TTP in central Norway during the 10-year study period. The prevalence of hereditary TTP in central Norway was 16.7 × 10(-6) persons. The most prevalent mutation was c.4143_4144dupA, accounting for two-thirds of disease causing alleles among patients and having an allelic frequency of 0.33% in the central, 0.10% in the western, and 0.04% in the southeastern Norwegian population. The allelic frequency of c.3178 C>T (p.R1060W) in the population was even higher (0.3-1%), but this mutation was infrequent among patients, with no homozygous cases. Conclusions We found a high prevalence of hereditary TTP in central Norway and an apparently different penetrance of ADAMTS-13 mutations.
UNLABELLED: Essentials The population prevalence of hereditary thrombotic thrombocytopenic purpura (TTP) is unknown. We studied the prevalence of hereditary TTP and population frequencies of two ADAMTS-13 mutations. A high frequency of hereditary TTP related to ADAMTS-13 mutation c.4143_4144dupA was found. Vicinity of ABO blood group and ADAMTS-13 loci may facilitate screening of ADAMTS-13 mutations. SUMMARY: Background Hereditary thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS-13 mutations is a rare, but serious condition. The prevalence is unknown, but it seems to be high in Norway. Objectives To identify all patients with hereditary TTP in central Norway and to investigate the prevalence of hereditary TTP and the population frequencies of two common ADAMTS-13 mutations. Patients/Methods Patients were identified in a cross-sectional study within the Central Norway Health Region by means of three different search strategies. Frequencies of ADAMTS-13 mutations, c.4143_4144dupA and c.3178 C>T (p.R1060W), were investigated in a population-based cohort (500 alleles) and in healthy blood donors (2104 alleles) by taking advantage of the close neighborhood of the ADAMTS-13 and ABO blood group gene loci. The observed prevalence of hereditary TTP was compared with the rates of ADAMTS-13 mutation carriers in different geographical regions. Results We identified 11 families with hereditary TTP in central Norway during the 10-year study period. The prevalence of hereditary TTP in central Norway was 16.7 × 10(-6) persons. The most prevalent mutation was c.4143_4144dupA, accounting for two-thirds of disease causing alleles among patients and having an allelic frequency of 0.33% in the central, 0.10% in the western, and 0.04% in the southeastern Norwegian population. The allelic frequency of c.3178 C>T (p.R1060W) in the population was even higher (0.3-1%), but this mutation was infrequent among patients, with no homozygous cases. Conclusions We found a high prevalence of hereditary TTP in central Norway and an apparently different penetrance of ADAMTS-13 mutations.
Authors: Hendrika A van Dorland; Magnus Mansouri Taleghani; Kazuya Sakai; Kenneth D Friedman; James N George; Ingrid Hrachovinova; Paul N Knöbl; Anne Sophie von Krogh; Reinhard Schneppenheim; Isabella Aebi-Huber; Lukas Bütikofer; Carlo R Largiadèr; Zuzana Cermakova; Koichi Kokame; Toshiyuki Miyata; Hideo Yagi; Deirdra R Terrell; Sara K Vesely; Masanori Matsumoto; Bernhard Lämmle; Yoshihiro Fujimura; Johanna A Kremer Hovinga Journal: Haematologica Date: 2019-02-21 Impact factor: 9.941
Authors: Nuno A G Graça; Bérangère S Joly; Jan Voorberg; Karen Vanhoorelbeke; Nicolas Béranger; Agnès Veyradier; Paul Coppo Journal: Br J Haematol Date: 2022-02-10 Impact factor: 8.615
Authors: Teresa Fidalgo; Patrícia Martinho; Catarina S Pinto; Ana C Oliveira; Ramon Salvado; Nina Borràs; Margarida Coucelo; Licínio Manco; Tabita Maia; M João Mendes; Rafael Del Orbe Barreto; Irene Corrales; Francisco Vidal; M Letícia Ribeiro Journal: Res Pract Thromb Haemost Date: 2017-06-23