Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network
| Autor: | López-Campos Bodineau, José Luis, Rapun, Noelia, Czischke, Karen, Jardim, José R, Fernandez Acquier, Mariano, ALÍ MUNIVE, ABRAHAM, Miravitlles, Marc |
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| Přispěvatelé: | 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, Seville, Spain. [Rapun N] 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. [Acquier MF] Servicio de Neumonología, Hospital Cetrángolo, Vicente López, Buenos Aires, Argentina. [Munive AA] Departamento Médico, Fundación Neumológica Colombiana, Bogotá, D.C., Colombia. [Miravitlles M] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Pulmons - Malalties
Genetic Phenomena::Genotype [PHENOMENA AND PROCESSES] enfermedades respiratorias::enfermedades pulmonares::deficiencia de alfa 1-antitripsina [ENFERMEDADES] Respiratory Tract Diseases::Lung Diseases::alpha 1-Antitrypsin Deficiency [DISEASES] Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [PHENOMENA AND PROCESSES] Genotip fenómenos genéticos::genotipo [FENÓMENOS Y PROCESOS] fenómenos genéticos::estructuras genéticas::genoma::componentes genómicos::genes::alelos [FENÓMENOS Y PROCESOS] Alfa 1-antitripsina |
| Zdroj: | Scientia |
| Popis: | Alpha1 antitrypsin deficiency; Diagnosis; Rare alleles Dèficit d'alfa1 antitripsina; Diagnòstic; Al·lels rars Déficit de alfa1 antitripsina; Diagnóstico; Alelos raros Background Knowledge of the frequency of rare SERPINA1 mutations could help in the management of alpha1 antitrypsin deficiency (AATD). The present study aims to assess the frequencies of rare and null alleles and their respiratory and hepatic pathogenicity. Methods This is a secondary analysis of a study that evaluated the viability of the Progenika diagnostic genotyping system in six different countries by analyzing 30,827 samples from cases of suspected AATD. Allele-specific genotyping was carried out with the Progenika A1AT Genotyping Test which analyses 14 mutations in buccal swabs or dried blood spots samples. SERPINA1 gene sequencing was performed for serum AAT-genotype discrepancies or by request of the clinician. Only cases with rare mutations were included in this analysis. Results There were 818 cases (2.6%) carrying a rare allele, excluding newly identified mutations. All were heterozygous except for 20 that were homozygous. The most frequent alleles were the M-like alleles, PI*Mmalton and PI*Mheerlen. Of the 14 mutations included in the Progenika panel, there were no cases detected of PI*Siiyama, PI*Q0granite falls and PI*Q0west. Other alleles not included in the 14-mutation panel and identified by gene sequencing included PI*Mwürzburg, PI*Zbristol, and PI*Zwrexham, and the null alleles PI*Q0porto, PI*Q0madrid, PI*Q0brescia, and PI*Q0kayseri. Conclusions The Progenika diagnostic network has allowed the identification of several rare alleles, some unexpected and not included in the initial diagnostic panel. This establishes a new perspective on the distribution of these alleles in different countries. These findings may help prioritize allele selection for routine testing and highlights the need for further research into their pathogenetic role. |
| Databáze: | OpenAIRE |
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