Publique en esta revista
Información de la revista
Vol. 54. Núm. 4.Abril 2018
Páginas 175-240
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 54. Núm. 4.Abril 2018
Páginas 175-240
Letter to the Editor
DOI: 10.1016/j.arbres.2017.10.006
Acceso a texto completo
Molecular Detection of the Frequent Allele F52del in Alpha 1 Antitrypsin Deficiency
Detección molecular del alelo F52del frecuente en la deficiencia de alfa-1-antitripsina
Visitas
306
Francisco Martínez Bugalloa,
Autor para correspondencia
fmarbug@gobiernodecanarias.org

Corresponding author.
, Juan Marco Figueira Gonçalvesb, María Dolores Martín Martíneza
a Human Genetic Unit, Clinical Analyses Services, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
b Pneumology and Thoracic Surgery Service, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
Este artículo ha recibido
306
Visitas
Información del artículo
Texto Completo
Bibliografía
Descargar PDF
Estadísticas
Tablas (1)
Table 1. Genotypes of Subjects with Rare Deficiency Alleles.
Dear Editor,
Texto Completo

In some recent issues, such as that of Belmonte et al.1 published in the International Journal of COPD, have incorporated of the Mmalton allele-specific genotyping assay in the diagnostic algorithm of alpha-1 antitrypsin deficiency (AATD) to allow the clinical characterization of Mmalton individuals.

Current laboratory tests for AATD involve the determination of a combination of alpha-1 antitrypsin (AAT) serum levels, AAT phenotyping by isoelectric focusing, and an allele specific genotyping assay to detect the most prevalent, S and Z, deficiency alleles.2 However, rare variants can only be detected by more complex techniques, such as the use of allelic specific probes or sequencing of the SERPINA1 gene, which are not available in all routine laboratories.

A study published by Martinez Bugallo et al.3 emphasizes that the Mmalton variant in the third most frequent variant deficiency in our island, after S and Z alleles, and with a higher prevalence than that described in the Iberian Peninsula. Forty two patients with AAT values <100mg/dL and with an inconclusive result in the genotype for PI*S and PI*Z underwent complete sequencing of the SERPINA1 gene. Of the 42 patients studied, at least one infrequent deficient allele was detected in 90.4% of the cases (38 patients). The most common deficient variant was Mmalton allele (64.2%), followed by Mpalermo allele (16.6%), both caused by the F52del mutation (Table 1).

Table 1.

Genotypes of Subjects with Rare Deficiency Alleles.

Genotype  N 
PI*M/Mmalton  17  40.4 
PI*S/Mmalton  16.6 
PI*Z/Mmalton  2.4 
PI*Mmalton/Mmalton  4.8 
PI*M/Mpalermo  14.3 
PI*S/Mpalermo  2.4 
PI*M/Q0amersfoort  2.4 
PI*Z/Q0amersfoort  2.4 
PI*Z/Q0cardiff  2.4 
PI*MI  2.4 
No deficitary allele  9.5 
Overall  42  100 

The Mmalton and Mpalermo are two rare variants characterized by an F52del (c.226_228delTTC) mutation. While the Mmalton allele must have derived from the normal M2 allele, Mpalermo derives from the normal M1V.4,5

In our population, Mpalermo represents 1 in 5 individuals with the F52del mutation, and although the use of specific probes for the detection of this mutation seems to be a good diagnostic strategy, it should be used as screening, since that in our opinion it is necessary to perform the complete sequencing of SERPINA1 in all cases to make a more accurate diagnosis of these variants, being necessary to confirm the presence of the base allele M2 or M1V in cis in these patients.

References
[1]
I. Belmonte, M. Barrecheguren, R.M. López-Martínez, C. Esquinas, E. Rodríguez, M. Miravitlles
Application of a diagnostic algorithm for the rare deficient variant Mmalton of alpha-1-antitrypsin deficiency: a new approach
Int J Chron Obstruct Pulmon Dis, 11 (2016), pp. 2535-2541 http://dx.doi.org/10.2147/COPD.S115940
[2]
M.R. Snyder, J.A. Katzmann, M.L. Butz, P. Yang, D.B. Dawson, K.C. Halling
Diagnosis of alpha-1-antitrypsin deficiency: an algorithm of quantification, genotyping, and phenotyping
Clin Chem, 52 (2006), pp. 2236-2242 http://dx.doi.org/10.1373/clinchem.2006.072991
[3]
F. Martínez Bugallo, J.M. Figueira Gonçalves, M.D. Martín Martínez, D. Díaz Pérez
Spectrum of alpha-1 antitrypsin deficiency mutations detected in Tenerife
Arch Bronconeumol, 53 (2017), pp. 595-596 http://dx.doi.org/10.1016/j.arbres.2017.03.005
[4]
D.T. Curiel, M.D. Holmes, H. Okayama, M.L. Brantly, C. Vogelmeier, W.D. Travis
Molecular basis of the liver and lung disease associated with the alpha 1-antitrypsin deficiency allele Mmalton
J Biol Chem, 264 (1989), pp. 13938-13945
[5]
P. Joly, O. Guillaud, V. Hervie, A. Francina, J.F. Mornex, C. Chapuis-Cellier
Clinical heterogeneity and potential high pathogenicity of the Mmalton Alpha 1 antitrypsin allele at the homozygous, compound heterozygous and heterozygous state
Orphanet J Rare Dis, 10 (2015), pp. 130 http://dx.doi.org/10.1186/s13023-015-0350-6
Copyright © 2017. SEPAR
Idiomas
Archivos de Bronconeumología

Suscríbase al Newsletter

Opciones de artículo
Herramientas
es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?