Avtor/Urednik		Germenis, Anastasios E.; Rijavec, Matija; Lopes Veronez, Camila
Naslov		Leveraging genetics for hereditary angioedema
Tip		članek
Vol. in št.		Letnik 60, št. 3
Leto izdaje		2021
Obseg		str. 416-428
ISSN		1559-0267 - Clinical reviews in allergy & immunology
Jezik		eng
Abstrakt		Biochemical studies performed during the last decades resulted in the development of various innovative medicinal products for hereditary angioedema (HAE). These therapeutic agents target the production or the function of bradykinin - the main mediator of HAE due to C1-inhibitor (C1-INH) deficiency. However, despite these remarkable achievements, current knowledge cannot provide convincing explanations for the clinical variability of the disease. As a consequence, treatment indications apply for drugs available for C1-INH deficiency. The advent of high-throughput next-generation sequencing technologies may assist in covering the missing part of our understanding of HAE pathogenesis. During the last 3 years alone, several new entities were added to the already described genotypes. The recent discovery of four novel target genes expands our understanding of other causes which may explain recurrent angioedema in individuals and families with normal C1-INH activity. Furthermore, new genetic technologies allowed the recognition of deep intronic variants associated with the disease, and elegant functional studies characterized new variants for the C1-INH gene. Thus, evidence has been provided regarding pathogenetic aspects remaining obscure for many years, such as the defective intracellular transport of mutant C1-INH, and environmental effect on the disease expression. Therefore, it seems that the stage for Precision Medicine era in HAE management is ready. Disease endotypes are expected to be uncovered and specified targets for therapeutic intervention will be detected, promising a more effective, individualized management of the disease.
Deskriptorji		Angioedemas, hereditary Genomics Precision medicine Hereditarni angioedemi Genomika Personalizirana medicina Genetics Genetika
Proste vsebinske oznake		pomanjkanje zaviralca C1 sekvenciranje nove generacije C1-inhibitor deficiency next-generation sequencing