Autoren:	Adenaeuer, Anke Ezigbo, D. Eyiuche Nazir, Hanan Fawzy Barco, Stefano Trinchero, Alice Laubert-Reh, Dagmar Strauch, Konstantin Wild, Philipp S. Lackner, Karl J. Lämmle, Bernhard Rossmann, Heidi
Titel:	c.451dupT in KLKB1 is common in Nigerians, confirming a higher prevalence of severe prekallikrein deficiency in Africans compared to Europeans
Online-Publikationsdatum:	5-Jul-2021
Erscheinungsdatum:	2021
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	BACKGROUND Severe prekallikrein deficiency (PK deficiency) is an autosomal-recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Africans according to gnomAD (allele frequency 1.43%). PATIENTS/METHODS The most common African (c.451dupT) and European (c.1643G>A, p.Cys548Tyr) PK deficiency causing KLKB1 variants were analyzed in two population-based collectives of 300 Nigerian and 300 German subjects. Genome databases were evaluated for variant frequencies and ethnicity of the subjects. The geographic origin of PK-deficient cases due to 451dupT was assessed. RESULTS Two of five patients with PK deficiency caused by homozygous 451dupT were African, one African American, one from Oman, and one of unknown origin. The frequency of 451dupT was 1.17% in the Nigerian collective (7/600 alleles); none had Cys548Tyr. Subjects with 451dupT were found among different Nigerian ethnicities. Both variants were absent in the European collective. Database research was compatible with these findings, even though mainly data of African Americans (451dupT: 1.12%-1.78%) was accessible. A relevant number of non-American Africans are included only in the 1000Genomes collective: 451dupT frequency was 1.29% in native Africans and 1.56% in African Caribbeans. CONCLUSIONS This study underlines the higher prevalence of PK deficiency among people with African descent compared to Europeans. In order to avoid delay of necessary surgical procedures in patients of African origin, diagnostic algorithms for isolated, unexplained, activated partial thromboplastin time prolongation in these subjects should include PK deficiency screening.
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-6169
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY-NC-ND
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by-nc-nd/4.0/
Zeitschrift:	Journal of thrombosis and haemostasis 19 1
Seitenzahl oder Artikelnummer:	147 152
Verlag:	Wiley-Blackwell
Verlagsort:	Oxford
Erscheinungsdatum:	2021
ISSN:	1538-7836
URL der Originalveröffentlichung:	https://doi.org/10.1111/jth.15137
DOI der Originalveröffentlichung:	10.1111/jth.15137
Enthalten in den Sammlungen:	JGU-Publikationen