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

• Published in: Journal of medical Internet research Vol. 22; no. 10; p. e19040
• Main Authors: Mendoza-Alvarez, Alejandro, Muñoz-Barrera, Adrián, Rubio-Rodríguez, Luis Alberto, Marcelino-Rodriguez, Itahisa, Corrales, Almudena, Iñigo-Campos, Antonio, Callero, Ariel, Perez-Rodriguez, Eva, Garcia-Robaina, Jose Carlos, González-Montelongo, Rafaela, Lorenzo-Salazar, Jose Miguel, Flores, Carlos
• Format: Journal Article
• Language: English
• Published: Canada Gunther Eysenbach MD MPH, Associate Professor 09.10.2020; JMIR Publications
• Subjects: Angioedema; Angioedemas, Hereditary - genetics; Angioedemas, Hereditary - therapy; Annotations; Classification; Databases, Genetic - standards; Edema; Genetic testing; Genetic Variation - genetics; Genomics; Humans; Internet; Medical diagnosis; Medical genetics; Misdiagnosis; Original Paper; Precision medicine; Validity; Variants; hereditary angioedema; precision medicine; genetic cause; knowledge database; variant interpretation
• ISSN: 1438-8871; 1439-4456; 1438-8871
• DOI: 10.2196/19040

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. 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). 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. 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. 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.