Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency

Alpha-1-antitrypsin deficiency (AATD) is associated with a high risk for the development of early-onset emphysema and liver disease. A large majority of subjects with severe AATD carry the ZZ genotype, which can be easily detected. Another rare pathologic variant, the Mmalton allele, causes a defici...

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Autores: Belmonte, Irene|||0000-0002-8675-8343, Barrecheguren, Miriam|||0000-0002-6041-1499, López-Martínez, Rosa M., Esquinas, Cristina|||0000-0001-5568-257X, Rodríguez González, Esther, Miravitlles, Marc|||0000-0002-9850-9520, Rodríguez Frías, Francisco|||0000-0002-9128-7013
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:186035
Acceso en línea:https://ddd.uab.cat/record/186035
https://dx.doi.org/urn:doi:10.2147/COPD.S115940
Access Level:acceso abierto
Palabra clave:Rare variant
Emphysema
Genotyping
Phenotyping
Serum levels
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spelling Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiencya new approachBelmonte, Irene|||0000-0002-8675-8343Barrecheguren, Miriam|||0000-0002-6041-1499López-Martínez, Rosa M.Esquinas, Cristina|||0000-0001-5568-257XRodríguez González, EstherMiravitlles, Marc|||0000-0002-9850-9520Rodríguez Frías, Francisco|||0000-0002-9128-7013Rare variantEmphysemaGenotypingPhenotypingSerum levelsAlpha-1-antitrypsin deficiency (AATD) is associated with a high risk for the development of early-onset emphysema and liver disease. A large majority of subjects with severe AATD carry the ZZ genotype, which can be easily detected. Another rare pathologic variant, the Mmalton allele, causes a deficiency similar to that of the Z variant, but it is not easily recognizable and its detection seems to be underestimated. Therefore, we have included a rapid allele-specific genotyping assay for the detection of the Mmalton variant in the diagnostic algorithm of AATD used in our laboratory. The objective of this study was to test the usefulness of this new algorithm for Mmalton detection. We performed a retrospective revision of all AATD determinations carried out in our laboratory over 2 years using the new diagnostic algorithm. Samples with a phenotype showing one or two M alleles and AAT levels discordant with that phenotype were analyzed using the Mmalton allele-specific genotyping assay. We detected 49 samples with discordant AAT levels; 44 had the MM and five the MS phenotype. In nine of these samples, a single rare Mmalton variant was detected. During the study period, two family screenings were performed and four additional Mmalton variants were identified. The incorporation of the Mmalton allele-specific genotyping assay in the diagnostic algorithm of AATD resulted in a faster and cheaper method to detect this allele and avoided a significant delay in diagnosis when a sequencing assay was required. This methodology can be adapted to other rare variants. Standardized algorithms are required to obtain conclusive data of the real incidence of rare AAT alleles in each region.Universitat Autònoma de Barcelona 22016-01-0120162016-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/186035https://dx.doi.org/urn:doi:10.2147/COPD.S115940reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1860352026-06-06T12:50:31Z
dc.title.none.fl_str_mv Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency
a new approach
title Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency
spellingShingle Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency
Belmonte, Irene|||0000-0002-8675-8343
Rare variant
Emphysema
Genotyping
Phenotyping
Serum levels
title_short Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency
title_full Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency
title_fullStr Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency
title_full_unstemmed Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency
title_sort Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency
dc.creator.none.fl_str_mv Belmonte, Irene|||0000-0002-8675-8343
Barrecheguren, Miriam|||0000-0002-6041-1499
López-Martínez, Rosa M.
Esquinas, Cristina|||0000-0001-5568-257X
Rodríguez González, Esther
Miravitlles, Marc|||0000-0002-9850-9520
Rodríguez Frías, Francisco|||0000-0002-9128-7013
author Belmonte, Irene|||0000-0002-8675-8343
author_facet Belmonte, Irene|||0000-0002-8675-8343
Barrecheguren, Miriam|||0000-0002-6041-1499
López-Martínez, Rosa M.
Esquinas, Cristina|||0000-0001-5568-257X
Rodríguez González, Esther
Miravitlles, Marc|||0000-0002-9850-9520
Rodríguez Frías, Francisco|||0000-0002-9128-7013
author_role author
author2 Barrecheguren, Miriam|||0000-0002-6041-1499
López-Martínez, Rosa M.
Esquinas, Cristina|||0000-0001-5568-257X
Rodríguez González, Esther
Miravitlles, Marc|||0000-0002-9850-9520
Rodríguez Frías, Francisco|||0000-0002-9128-7013
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Rare variant
Emphysema
Genotyping
Phenotyping
Serum levels
topic Rare variant
Emphysema
Genotyping
Phenotyping
Serum levels
description Alpha-1-antitrypsin deficiency (AATD) is associated with a high risk for the development of early-onset emphysema and liver disease. A large majority of subjects with severe AATD carry the ZZ genotype, which can be easily detected. Another rare pathologic variant, the Mmalton allele, causes a deficiency similar to that of the Z variant, but it is not easily recognizable and its detection seems to be underestimated. Therefore, we have included a rapid allele-specific genotyping assay for the detection of the Mmalton variant in the diagnostic algorithm of AATD used in our laboratory. The objective of this study was to test the usefulness of this new algorithm for Mmalton detection. We performed a retrospective revision of all AATD determinations carried out in our laboratory over 2 years using the new diagnostic algorithm. Samples with a phenotype showing one or two M alleles and AAT levels discordant with that phenotype were analyzed using the Mmalton allele-specific genotyping assay. We detected 49 samples with discordant AAT levels; 44 had the MM and five the MS phenotype. In nine of these samples, a single rare Mmalton variant was detected. During the study period, two family screenings were performed and four additional Mmalton variants were identified. The incorporation of the Mmalton allele-specific genotyping assay in the diagnostic algorithm of AATD resulted in a faster and cheaper method to detect this allele and avoided a significant delay in diagnosis when a sequencing assay was required. This methodology can be adapted to other rare variants. Standardized algorithms are required to obtain conclusive data of the real incidence of rare AAT alleles in each region.
publishDate 2016
dc.date.none.fl_str_mv 2
2016-01-01
2016
2016-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/186035
https://dx.doi.org/urn:doi:10.2147/COPD.S115940
url https://ddd.uab.cat/record/186035
https://dx.doi.org/urn:doi:10.2147/COPD.S115940
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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