Autoren:	Barco, Stefano Sollfrank, Stefanie Trinchero, Alice Adenaeuer, Anke AbolghasemI, Hassan Conti, Laura Häuser, Friederike Kremer Hovinga, Johanna A. Lackner, Karl J. Loewecke, Felicia Miloni, Erwin Vazifeh Shiran, Nader Tomao, Luigi Wuillemin, Walter A. Zieger, Barbara Lämmle, Bernhard Rossmann, Heidi
Titel:	Severe plasma prekallikrein deficiency : clinical characteristics, novel KLKB1 mutations, and estimated prevalence
Online-Publikationsdatum:	17-Aug-2021
Erscheinungsdatum:	2020
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	BACKGROUND Severe plasma prekallikrein (PK) deficiency is an autosomal-recessive defect characterized by isolated activated partial thromboplastin time prolongation. To date, no comprehensive methodologically firm analysis has investigated the diagnostic, clinical, and genetic characteristics of PK deficiency, and its prevalence remains unknown. PATIENTS/METHODS We described new families with PK deficiency, retrieved clinical and laboratory information of cases systematically searched in the (gray) literature, and collected blood of these cases for complementary analyses. The Genome Aggregation Database (gnomAD) and the population-based Gutenberg Health Study served to study the prevalence of mutations and relevant genetic variants. RESULTS We assembled a cohort of 111 cases from 89 families and performed new genetic analyses in eight families (three unpublished). We identified new KLKB1 mutations, excluded the pathogenicity of some of the previously described ones, and estimated a prevalence of severe PK deficiency of 1/155 668 overall and 1/4725 among Africans. One individual reported with PK deficiency had, in fact, congenital kininogen deficiency associated with decreased PK activity. One quarter of individuals had factor XII clotting activity below the reference range. Four major bleeding events were described in 96 individuals, of which 3 were provoked, for a prevalence of 4% and an annualized rate of 0.1%. The prevalence of cardiovascular events was 15% (6% <40 years; 21% 40-65 years; 33% >65 years) for an annualized rate of 0.4%. CONCLUSIONS We characterized the genetic background of severe PK deficiency, critically appraised mutations, and provided prevalence estimates. Our data on laboratory characteristics and clinical course of severe PK deficiency may have clinical implications.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-6292
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY-NC
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by-nc/4.0/
Zeitschrift:	Journal of thrombosis and haemostasis 18 7
Seitenzahl oder Artikelnummer:	1598 1617
Verlag:	Wiley-Blackwell
Verlagsort:	Oxford
Erscheinungsdatum:	2020
ISSN:	1538-7836
URL der Originalveröffentlichung:	https://doi.org/10.1111/jth.14805
DOI der Originalveröffentlichung:	10.1111/jth.14805
Enthalten in den Sammlungen:	JGU-Publikationen