Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis

Autor: José Luis, Lopez-Campos, Lourdes, Osaba, Karen, Czischke, José R, Jardim, Mariano, Fernandez Acquier, Abraham, Ali, Hakan, Günen, Noelia, Rapun, Estrella, Drobnic, Marc, Miravitlles
Přispěvatelé: Grifols, Institut Català de la Salut, [Lopez-Campos JL] Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. [Osaba L] Progenika Biopharma, a Grifols Company, Derio, Vizcaya, Spain. [Czischke K] Departamento de Neumología, Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile. [Jardim JR] Centro de Reabilitação Pulmonar da Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM/Unifesp), São Paulo, Brazil. [Fernandez Acquier M] Servicio de Neumonología, Hospital Cetrángolo, Vicente López, Buenos Aires, Argentina. [Ali A] Departamento Médico, Fundación Neumológica Colombiana, Bogotá, D.C., Colombia. [Miravitlles M] CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2022
Předmět:
Genotyping
Respiratory Tract Diseases::Lung Diseases::Lung Diseases
Obstructive::Pulmonary Disease
Chronic Obstructive [DISEASES]
Genotype
Pulmons - Malalties obstructives
Otros calificadores::/diagnóstico [Otros calificadores]
fenómenos genéticos::genotipo [FENÓMENOS Y PROCESOS]
Alfa 1-antitripsina
enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedad pulmonar obstructiva crónica [ENFERMEDADES]
Genetic Phenomena::Genotype [PHENOMENA AND PROCESSES]
Pulmonary Disease
Chronic Obstructive
Alpha1 antitrypsin deficiency
Cross-Sectional Studies
enfermedades respiratorias::enfermedades pulmonares::deficiencia de alfa 1-antitripsina [ENFERMEDADES]
Dried blood spots
Digestive System Diseases::Liver Diseases::alpha 1-Antitrypsin Deficiency [DISEASES]
alpha 1-Antitrypsin
alpha 1-Antitrypsin Deficiency
Diagnosis
Other subheadings::/diagnosis [Other subheadings]
Buccal swab
Feasibility Studies
Humans
Genotip
Alleles
Zdroj: Scientia
ISSN: 1465-993X
DOI: 10.1186/s12931-022-02074-x
Popis: [Introduction] Currently, strategies for improving alpha1 antitrypsin deficiency (AATD) diagnosis are needed. Here we report the performance of a multinational multiplex-based genotyping test on dried blood spots and buccal swabs sent by post or courier and with web registration for subjects with suspected AATD in Argentina, Brazil, Chile, Colombia, Spain, and Turkey.
[Methods] This was an observational, cross-sectional analysis of samples from patients with suspected AATD from March 2018 to January 2022. Samples were coded on a web platform and sent by post or courier to the central laboratory in Northern Spain. Allele-specific genotyping for the 14 most common mutations was carried out with the A1AT Genotyping Test (Progenika-Grifols, Spain). SERPINA1 gene sequencing was performed if none of the mutations were found or one variant was detected in heterozygous status and the AAT serum level was
[Results] The study included 30,827 samples: 30,458 (94.7%) with final results after direct genotyping and 369 (1.1%) with additional gene sequencing. Only 0.3% of the samples were not processed due to their poor quality. The prevalence of the most frequent allele combinations was MS 14.7%, MZ 8.6%, SS 1.9%, SZ 1.9%, and ZZ 0.9%. Additionally, 70 cases with new mutations were identified. Family screening was conducted in 2.5% of the samples. Samples from patients with respiratory diseases other than COPD, including poorly controlled asthma or bronchiectasis, also presented AATD mutations.
[Conclusions] Our results confirm the viability of this diagnostic system for genotyping AATD conducted simultaneously in different countries. The system has proved satisfactory and can improve the timely diagnosis of AATD.
This project is entirely funded by Grifols.
Databáze: OpenAIRE
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