Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency : a new approach
Belmonte, Irene (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Barrecheguren, Miriam (Hospital Universitari Vall d'Hebron)
López-Martínez, Rosa M. (Hospital Universitari Vall d'Hebron)
Esquinas, Cristina (Hospital Universitari Vall d'Hebron)
Rodríguez González, Esther (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Miravitlles, Marc (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Rodríguez Frías, Francisco (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Universitat Autònoma de Barcelona

Data:	2016
Resum:	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.
Nota:	Ajuts: grant from the Fundación Catalana de Pneumología (FUCAP 2014), funding from Grifols to the Catalan Center for Research in AATD of the Vall d'Hebron Research Institute
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Rare variant ; Emphysema ; Genotyping ; Phenotyping ; Serum levels
Publicat a:	International journal of COPD, Vol. 11, Num. 1 (October 2016) , p. 2535-2541, ISSN 1178-2005

DOI: 10.2147/COPD.S115940
PMID: 27877030

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