Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation

• DOI: 10.2196/19040
• Publication Date: 2020-10-09T14:00:42Z
• Authors: Alejandro Mendoza...; Adrián Muñoz-Barrera; Luis Alberto Rubi...; Itahisa Marcelino...; Almudena Corrales; Antonio Iñigo-Campos; Ariel Callero; Eva Perez-Rodriguez; Jose Carlos Garci...; Rafaela González-...; Jose Miguel Loren...; Carlos Flores
• Keywords: 0301 basic medicine; Original Paper; Internet; 0303 health sciences; Computer applications to medicine. Medical informatics; R858-859.7; Angioedemas, Hereditary; Genetic Variation; 3. Good health; 03 medical and health sciences; Databases, Genetic; Humans; Public aspects of medicine; RA1-1270

Background Hereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, first-line genetic screening is not integrated in routine diagnosis. Consequently, a delay in the diagnosis, and inaccurate or incomplete diagnosis and treatment of hereditary angioedema are common.

Objective In agreement with recent recommendations from the International Consensus on the Use of Genetics in the Management of Hereditary Angioedema, to facilitate the clinical diagnosis and adapt it to the paradigm of precision medicine and next-generation sequencing–based genetic tests, we aimed to develop a genetic annotation tool, termed Hereditary Angioedema Database Annotation (HADA).

Methods HADA is built on top of a database of known variants affecting function, including precomputed pathogenic assessment of each variant and a ranked classification according to the current guidelines from the American College of Medical Genetics and Genomics.

Results HADA is provided as a freely accessible, user-friendly web-based interface with versatility for the entry of genetic information. The underlying database can also be incorporated into automated command-line stand-alone annotation tools.

Conclusions HADA can achieve the rapid detection of variants affecting function for different hereditary angioedema types, and further integrates useful information to reduce the diagnosis odyssey and improve its delay.