Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort

Background: The optimal serum alpha-1 antitrypsin (AAT) cut-off for prompting genotyping in alpha-1 antitrypsin deficiency (AATD) remains debated, with limited data on mutations missed at different thresholds. This study assessed the frequency and spectrum of mutations potentially overlooked when ap...

Descripción completa

Detalles Bibliográficos
Autores: López-Campos Bodineau, José Luis, Muñoz Sánchez, Belén, Fernández Boza, Alba, Quintana Gallego, María Esther
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:dnet:idus________::5fc32ae9b4a619d906ea0667101fd087
Acceso en línea:https://hdl.handle.net/11441/185371
https://doi.org/10.1080/25310429.2026.2652160
Access Level:acceso abierto
Palabra clave:Alpha-1 antitrypsin deficiency
Serum cut-off
Genetic mutations
Screening
Diagnosis
id ES_b92bbc8704c3092ee958bdde48799c8b
oai_identifier_str oai:dnet:idus________::5fc32ae9b4a619d906ea0667101fd087
network_acronym_str ES
network_name_str España
repository_id_str
spelling Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohortLópez-Campos Bodineau, José LuisMuñoz Sánchez, BelénFernández Boza, AlbaQuintana Gallego, María EstherAlpha-1 antitrypsin deficiencySerum cut-offGenetic mutationsScreeningDiagnosisBackground: The optimal serum alpha-1 antitrypsin (AAT) cut-off for prompting genotyping in alpha-1 antitrypsin deficiency (AATD) remains debated, with limited data on mutations missed at different thresholds. This study assessed the frequency and spectrum of mutations potentially overlooked when applying varying serum AAT values. Methods: Data were analysed from the Andalusian Valuable and Transdisciplinary AATD Registry (AVATAR), a prospective cohort undergoing standardised AATD evaluation. Serum AAT and C-reactive protein were measured, followed by SERPINA1 genotyping. Mutation detection rates were examined at thresholds of 90, 100, 110, 116, and 120 mg/dL. Results: Among 492 participants (mean age 53.8 years; 53.0% male), 320 (65.0%) carried at least one mutation, most frequently PIMS (29.7%) and PIMZ (18.1%). At 90 mg/dL, 188 individuals (52.5%) above this value still harboured mutations, including 36 (10.0%) with potentially severe genotypes. Raising the threshold progressively reduced missed mutations, but no PIZZ or PISZ cases were found above any cut-off. Conclusions: Serum AAT threshold selection substantially affects mutation detection. Lower thresholds prioritise severe genotypes, while higher thresholds capture more carriers, facilitating cascade screening but increasing workload. Thresholds should be tailored to the clinical and public health aims of screening.Taylor and Francis GroupMedicinaInstituto de Salud Carlos IIIGobierno de España2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/185371https://doi.org/10.1080/25310429.2026.2652160reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésPulmonology, 32 (1), 2652160. CB17-06-00030info:eu-repo/semantics/openAccessoai:dnet:idus________::5fc32ae9b4a619d906ea0667101fd0872026-06-17T12:51:07Z
dc.title.none.fl_str_mv Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort
title Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort
spellingShingle Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort
López-Campos Bodineau, José Luis
Alpha-1 antitrypsin deficiency
Serum cut-off
Genetic mutations
Screening
Diagnosis
title_short Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort
title_full Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort
title_fullStr Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort
title_full_unstemmed Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort
title_sort Undetected mutations across different serum alpha1 antitrypsin thresholds: An analysis of the avatar cohort
dc.creator.none.fl_str_mv López-Campos Bodineau, José Luis
Muñoz Sánchez, Belén
Fernández Boza, Alba
Quintana Gallego, María Esther
author López-Campos Bodineau, José Luis
author_facet López-Campos Bodineau, José Luis
Muñoz Sánchez, Belén
Fernández Boza, Alba
Quintana Gallego, María Esther
author_role author
author2 Muñoz Sánchez, Belén
Fernández Boza, Alba
Quintana Gallego, María Esther
author2_role author
author
author
dc.contributor.none.fl_str_mv Medicina
Instituto de Salud Carlos III
Gobierno de España
dc.subject.none.fl_str_mv Alpha-1 antitrypsin deficiency
Serum cut-off
Genetic mutations
Screening
Diagnosis
topic Alpha-1 antitrypsin deficiency
Serum cut-off
Genetic mutations
Screening
Diagnosis
description Background: The optimal serum alpha-1 antitrypsin (AAT) cut-off for prompting genotyping in alpha-1 antitrypsin deficiency (AATD) remains debated, with limited data on mutations missed at different thresholds. This study assessed the frequency and spectrum of mutations potentially overlooked when applying varying serum AAT values. Methods: Data were analysed from the Andalusian Valuable and Transdisciplinary AATD Registry (AVATAR), a prospective cohort undergoing standardised AATD evaluation. Serum AAT and C-reactive protein were measured, followed by SERPINA1 genotyping. Mutation detection rates were examined at thresholds of 90, 100, 110, 116, and 120 mg/dL. Results: Among 492 participants (mean age 53.8 years; 53.0% male), 320 (65.0%) carried at least one mutation, most frequently PIMS (29.7%) and PIMZ (18.1%). At 90 mg/dL, 188 individuals (52.5%) above this value still harboured mutations, including 36 (10.0%) with potentially severe genotypes. Raising the threshold progressively reduced missed mutations, but no PIZZ or PISZ cases were found above any cut-off. Conclusions: Serum AAT threshold selection substantially affects mutation detection. Lower thresholds prioritise severe genotypes, while higher thresholds capture more carriers, facilitating cascade screening but increasing workload. Thresholds should be tailored to the clinical and public health aims of screening.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/185371
https://doi.org/10.1080/25310429.2026.2652160
url https://hdl.handle.net/11441/185371
https://doi.org/10.1080/25310429.2026.2652160
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Pulmonology, 32 (1), 2652160.
CB17-06-00030
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor and Francis Group
publisher.none.fl_str_mv Taylor and Francis Group
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869417730666397697
score 15.812429

Similares en LA Referencia