Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network
Abstract 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 analy...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Human Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40246-023-00497-1 |
| _version_ | 1797806574293483520 |
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| author | José Luis Lopez-Campos Noelia Rapun Karen Czischke José R. Jardim Mariano Fernandez Acquier Abraham Ali Munive Hakan Günen Estrella Drobnic Marc Miravitlles Lourdes Osaba |
| author_facet | José Luis Lopez-Campos Noelia Rapun Karen Czischke José R. Jardim Mariano Fernandez Acquier Abraham Ali Munive Hakan Günen Estrella Drobnic Marc Miravitlles Lourdes Osaba |
| author_sort | José Luis Lopez-Campos |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-13T06:09:19Z |
| format | Article |
| id | doaj.art-64d74f862c284908abdd7fe4b2d7452d |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-03-13T06:09:19Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-64d74f862c284908abdd7fe4b2d7452d2023-06-11T11:20:14ZengBMCHuman Genomics1479-73642023-06-0117111210.1186/s40246-023-00497-1Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic networkJosé Luis Lopez-Campos0Noelia Rapun1Karen Czischke2José R. Jardim3Mariano Fernandez Acquier4Abraham Ali Munive5Hakan Günen6Estrella Drobnic7Marc Miravitlles8Lourdes Osaba9Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de SevillaProgenika Biopharma, a Grifols Company. DerioDepartamento de Neumología, Clínica Alemana de Santiago, Universidad del DesarrolloCentro de Reabilitação Pulmonar da Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM/Unifesp)Servicio de Neumonología, Hospital Cetrángolo, Vicente LópezDepartamento Médico, Fundación Neumológica ColombianaUniversity of Health Sciences, Süreyyapaşa Research and Training Center for Chest Diseases and Thoracic SurgeryScientific & Medical AffairsServicio de Neumología, Hospital Universitari Vall d’Hebron/Vall d’Hebron Research Institute (VHIR)Progenika Biopharma, a Grifols Company. DerioAbstract 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.https://doi.org/10.1186/s40246-023-00497-1Alpha1 antitrypsin deficiencyDiagnosisRare allelesNull allelesFrequency |
| spellingShingle | José Luis Lopez-Campos Noelia Rapun Karen Czischke José R. Jardim Mariano Fernandez Acquier Abraham Ali Munive Hakan Günen Estrella Drobnic Marc Miravitlles Lourdes Osaba Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network Human Genomics Alpha1 antitrypsin deficiency Diagnosis Rare alleles Null alleles Frequency |
| title | Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network |
| title_full | Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network |
| title_fullStr | Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network |
| title_full_unstemmed | Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network |
| title_short | Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network |
| title_sort | distribution of alpha1 antitrypsin rare alleles in six countries results from the progenika diagnostic network |
| topic | Alpha1 antitrypsin deficiency Diagnosis Rare alleles Null alleles Frequency |
| url | https://doi.org/10.1186/s40246-023-00497-1 |
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