Real-world clinical applicability of pathogenicity predictors assessed on SERPINA1 mutations in alpha-1-antitrypsin deficiency

Human Mutation

Volumn 39, Issue 9, 2018, Pages 1203-1213

  Giacopuzzi, Edoardo ^a   Laffranchi, Mattia ^a   Berardelli, Romina ^a   Ravasio, Viola ^a   Ferrarotti, Ilaria ^b   Gooptu, Bibek ^c   Borsani, Giuseppe ^a   Fra, Annamaria ^a  

^a UNIVERSITY OF BRESCIA   (Italy)

^b UNIVERSITY OF PAVIA   (Italy)

^c UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

alpha 1 antitrypsin deficiency; alpha 1 antitrypsin polymers; ExAC database; pathogenicity prediction; serpinopathies; serpins

Indexed keywords

ALPHA 1 ANTITRYPSIN; STRUCTURAL PROTEIN; LEUKOCYTE ELASTASE; SERPINA1 PROTEIN, HUMAN;

ALPHA 1 ANTITRYPSIN DEFICIENCY; ARTICLE; ENZYME LINKED IMMUNOSORBENT ASSAY; EXPRESSION VECTOR; GENE; GENE FREQUENCY; GENETIC CODE; GENETIC TRANSFECTION; GENETIC VARIABILITY; HUMAN; HUMAN CELL; LIMIT OF QUANTITATION; MISSENSE MUTATION; NATIVE POLYACRYLAMIDE GEL ELECTROPHORESIS; PATHOPHYSIOLOGY; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; SERPINA1 GENE; ALLELE; BIOLOGY; ENDOPLASMIC RETICULUM; EXOME; FEMALE; GENETIC DATABASE; GENETICS; MALE; PATHOLOGY; POPULATION GENETICS; WHOLE EXOME SEQUENCING;

ALLELES; ALPHA 1-ANTITRYPSIN; ALPHA 1-ANTITRYPSIN DEFICIENCY; COMPUTATIONAL BIOLOGY; DATABASES, GENETIC; ENDOPLASMIC RETICULUM; EXOME; FEMALE; GENETICS, POPULATION; HUMANS; LEUKOCYTE ELASTASE; MALE; MUTATION, MISSENSE; WHOLE EXOME SEQUENCING;

EID: 85052539364     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.23562     Document Type: Article

References (52)

1. Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., … Sunyaev, S. R. (2010). A method and server for predicting damaging missense mutations. Nature Methods, 7, 248–249
2. American Thoracic Society; European Respiratory Society (2003). American thoracic society/european respiratory society statement: Standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. American Journal of Respiratory and Critical Care Medicine, 168, 818–900
3. Cook, L., Burdon, J. G., Brenton, S., Knight, K. R., & Janus, E. D. (1996). Kinetic characterisation of alpha-1-antitrypsin F as an inhibitor of human neutrophil elastase. Pathology, 28, 242–247
4. Curiel, D. T., Chytil, A., Courtney, M., & Crystal, R. G. (1989). Serum alpha 1-antitrypsin deficiency associated with the common S-type (Glu264Val) mutation results from intracellular degradation of alpha 1-antitrypsin prior to secretion. Journal of Biological Chemistry, 264, 10477–10486
5. Faber, J. P., Poller, W., Weidinger, S., Kirchgesser, M., Schwaab, R., Bidlingmaier, F., & Olek, K. (1994). Identification and DNA sequence analysis of 15 new alpha 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele. American Journal of Human Genetics, 55, 1113–1121
6. Ferrarotti, I., Baccheschi, J., Zorzetto, M., Tinelli, C., Corda, L., Balbi, B., … Luisetti, M. (2005). Prevalence and phenotype of subjects carrying rare variants in the Italian registry for alpha1-antitrypsin deficiency. Journal of Medical Genetics, 42, 282–287
7. Ferrarotti, I., Carroll, T. P., Ottaviani, S., Fra, A. M., O'Brien, G., Molloy, K., … Luisetti, M. (2014). Identification and characterisation of eight novel SERPINA1 Null mutations. Orphanet Journal of Rare Diseases, 9, 172
8. Ferrarotti, I., Scabini, R., Campo, I., Ottaviani, S., Zorzetto, M., Gorrini, M., & Luisetti, M. (2007). Laboratory diagnosis of alpha1-antitrypsin deficiency. Translational Research, 150, 267–274
9. Fokkema, I. F. A.C., Taschner, P. E. M., Schaafsma, G. C. P., Celli, J., Laros, J. F. J., & den Dunnen, J. T. (2011). LOVD v.2.0: The next generation in gene variant databases. Human Mutation, 32, 557–563
10. Fra, A., Cosmi, F., Ordoñez, A., Berardelli, R., Perez, J., Guadagno, N. A., … Miranda, E. (2016). Polymers of Z α1-antitrypsin are secreted in cell models of disease. European Respiratory Journal, 47, 1005–1009
11. Fra, A., Yoboue, E. D., & Sitia, R. (2017). Cysteines as redox molecular switches and targets of disease. Frontiers in Molecular Neuroscience, 10, 167
12. Fra, A. M., Gooptu, B., Ferrarotti, I., Miranda, E., Scabini, R., Ronzoni, R., … Schiaffonati, L. (2012). Three new alpha1-antitrypsin deficiency variants help to define a C-terminal region regulating conformational change and polymerization. PLoS One, 7, e38405
13. Graham, A., Kalsheker, N. A., Newton, C. R., Bamforth, F. J., Powell, S. J., & Markham, A. F. (1989). Molecular characterisation of three alpha-1-antitrypsin deficiency variants: Proteinase inhibitor (Pi) nullcardiff (Asp256Val); PiMmalton (Phe51deletion) and PiI (Arg39Cys). Human Genetics, 84, 55–58
14. Haq, I., Irving, J. A., Saleh, A. D., Dron, L., Regan-Mochrie, G. L., Motamedi-Shad, N., … Lomas, D. A. (2016). Deficiency mutations of alpha-1 antitrypsin. effects on folding, function, and polymerization. American Journal of Respiratory Cell and Molecular Biology, 54, 71–80
15. Hazari, Y. M., Bashir, A., Habib, M., Bashir, S., Habib, H., Qasim, M. A., … Fazili, K. M. (2017). Alpha-1-antitrypsin deficiency: Genetic variations, clinical manifestations and therapeutic interventions. Mutation Research, 773, 14–25
16. Ioannidis, N. M., Rothstein, J. H., Pejaver, V., Middha, S., McDonnell, S. K., Baheti, S., … Sieh, W. (2016). REVEL: An ensemble method for predicting the pathogenicity of rare missense variants. American Journal of Human Genetics, 99, 877–885
17. Irving, J. A., Pike, R. N., Lesk, A. M., & Whisstock, J. C. (2000). Phylogeny of the serpin superfamily: Implications of patterns of amino acid conservation for structure and function. Genome Research, 10, 1845–1864
18. Jagadeesh, K. A., Wenger, A. M., Berger, M. J., Guturu, H., Stenson, P. D., Cooper, D. N., … Bejerano, G. (2016). M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity. Nature Genetics, 48, 1581–1586
19. Janciauskiene, S., Wrenger, S., Immenschuh, S., Olejnicka, B., Greulich, T., Welte, T., & Chorostowska-Wynimko, J. (2018). The multifaceted effects of alpha1-antitrypsin on neutrophil functions. Frontiers in Pharmacology, 9, 341
20. Joly, P., Lacan, P., Chapuis-Cellier, C., Garcia, C., Bererd, M., & Francina, A. (2014). Molecular characterization of 7 new alpha-1 anti-trypsin (A1AT) variants including two with an associated deficient phenotype. Clinica Chimica Acta, 427, 21–22
21. Joly, P., Vignaud, H., Di Martino, J., Ruiz, M., Garin, R., Restier, L., … Bouchecareilh, M. (2017). ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency. PLoS One, 12, e0179369
22. Jonigk, D., Al-Omari, M., Maegel, L., Müller, M., Izykowski, N., Hong, J., … Janciauskiene, S. (2013). Anti-inflammatory and immunomodulatory properties of α1-antitrypsin without inhibition of elastase. Proceedings of National Academy of Sciences United States of America, 110, 15007–15012
23. Kircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. (2014). A general framework for estimating the relative pathogenicity of human genetic variants. Nature Genetics, 46, 310–315
24. Laffranchi, M., Berardelli, R., Ronzoni, R., Lomas, D. A., & Fra, A. (2018). Heteropolymerization of α-1-antitrypsin mutants in cell models mimicking heterozygosity. Human Molecular Genetics, 27, 1785–1793
25. Landrum, M. J., Lee, J. M., Riley, G. R., Jang, W., Rubinstein, W. S., Church, D. M., & Maglott, D. R. (2014). ClinVar: Public archive of relationships among sequence variation and human phenotype. Nucleic Acids Research, 42, D980–985
26. Liu, X., Jian, X., & Boerwinkle, E. (2011). dbNSFP: A lightweight database of human nonsynonymous SNPs and their functional predictions. Human Mutation, 32, 894–899
27. Liu, X., Wu, C., Li, C., & Boerwinkle, E. (2016). dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs. Human Mutation, 37, 235–241
28. Lomas, D. A., Finch, J. T., Seyama, K., Nukiwa, T., & Carrell, R. W. (1993). Alpha 1-antitrypsin Siiyama (Ser53→Phe). Further evidence for intracellular loop-sheet polymerization. Journal of Biological Chemistry, 268, 15333–15335
29. Lomas, D. A., Hurst, J. R., & Gooptu, B. (2016). Update on alpha-1 antitrypsin deficiency: New therapies. Journal of Hepatology, 65, 413–424
30. Luisetti, M., & Seersholm, N. (2004). Alpha1-antitrypsin deficiency. 1: Epidemiology of alpha1-antitrypsin deficiency. Thorax, 59, 164–169
31. Masica, D. L., Sosnay, P. R., Cutting, G. R., & Karchin, R. (2012). Phenotype-optimized sequence ensembles substantially improve prediction of disease-causing mutation in cystic fibrosis. Human Mutation, 33, 1267–1274
32. Medicina, D., Montani, N., Fra, A. M., Tiberio, L., Corda, L., Miranda, E., … Schiaffonati, L. (2009). Molecular characterization of the new defective P(brescia) alpha1-antitrypsin allele. Human Mutation, 30, E771–781
33. Miranda, E., Ferrarotti, I., Berardelli, R., Laffranchi, M., Cerea, M., Gangemi, F., … Fra, A. (2017). The pathological Trento variant of alpha-1-antitrypsin (E75V) shows nonclassical behaviour during polymerization. FEBS Journal, 284, 2110–2126
34. Miranda, E., Pérez, J., Ekeowa, U. I., Hadzic, N., Kalsheker, N., Gooptu, B., … Lomas, D. A. (2010). A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with alpha1-antitrypsin deficiency. Hepatology, 52, 1078–1088
35. Niroula, A., Urolagin, S., & Vihinen, M. (2015). PON-P2: Prediction method for fast and reliable identification of harmful variants. PLoS One, 10, e0117380
36. Niroula, A., & Vihinen, M. (2016). Variation interpretation predictors: Principles, types, performance, and choice. Human Mutation, 37, 579–597
37. Nyon, M. P., Segu, L., Cabrita, L. D., Lévy, G. R., Kirkpatrick, J., Roussel, B. D., … Gooptu, B. (2012). Structural dynamics associated with intermediate formation in an archetypal conformational disease. Structure, 20, 504–512
38. Ogushi, F., Fells, G. A., Hubbard, R. C., Straus, S. D., & Crystal, R. G. (1987). Z-type alpha 1-antitrypsin is less competent than M1-type alpha 1-antitrypsin as an inhibitor of neutrophil elastase. Journal of Clinical Investigation, 80, 1366–1374
39. Okayama, H., Brantly, M., Holmes, M., & Crystal, R. G. (1991). Characterization of the molecular basis of the alpha 1-antitrypsin F allele. American Journal of Human Genetics, 48, 1154–1158
40. Owen, M. C., Brennan, S. O., Lewis, J. H., & Carrell, R. W. (1983). Mutation of antitrypsin to antithrombin. alpha 1-antitrypsin Pittsburgh (358 Met leads to Arg), a fatal bleeding disorder. New England Journal of Medicine, 309, 694–698
41. Piras, B., Ferrarotti, I., Lara, B., Martinez, M. T., Bustamante, A., Ottaviani, S., … Miravitlles, M. (2013). Clinical phenotypes of Italian and Spanish patients with α1-antitrypsin deficiency.European Respiratory Journal, 42, 54–64
42. Riera, C., Padilla, N., & de la Cruz, X. (2016). The Complementarity Between Protein-Specific and General Pathogenicity Predictors for Amino Acid Substitutions. Human Mutation, 37, 1013–1024
43. Ronzoni, R., Berardelli, R., Medicina, D., Sitia, R., Gooptu, B., & Fra, A. M. (2016). Aberrant disulphide bonding contributes to the ER retention of alpha1-antitrypsin deficiency variants. Human Molecular Genetics, 25, 642–650
44. Sala, A. J., Bott, L. C., & Morimoto, R. I. (2017). Shaping proteostasis at the cellular, tissue, and organismal level. Journal of Cell Biology, 216, 1231–1241
45. de Serres, F. J., & Blanco, I. (2012). Prevalence of α1-antitrypsin deficiency alleles PI*S and PI*Z worldwide and effective screening for each of the five phenotypic classes PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ: A comprehensive review. Therapeutic Advances in Respiratory Disease, 6, 277–295
46. Sing, T., Sander, O., Beerenwinkel, N., & Lengauer, T. (2005). ROCR: Visualizing classifier performance in R. Bioinformatics, 21, 3940–3941
47. Starita, L. M., Young, D. L., Islam, M., Kitzman, J. O., Gullingsrud, J., Hause, R. J., … Fields, S. (2015). Massively Parallel Functional Analysis of BRCA1 RING Domain Variants. Genetics, 200, 413–422
48. Stenson, P. D., Mort, M., Ball, E. V., Shaw, K., Phillips, A., & Cooper, D. N. (2014). The Human Gene Mutation Database: Building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Human Genetics, 133, 1–9
49. Tan, L., Dickens, J. A., Demeo, D. L., Miranda, E., Perez, J., Rashid, S. T., … Lomas, D. A. (2014). Circulating polymers in α1-antitrypsin deficiency. European Respiratory Journal, 43, 1501–1504
50. Tsutsui, Y., Cruz, R. D., & Wintrode, P. L. (2012). Folding mechanism of the metastable serpin α1-antitrypsin. PNAS, 109, 4467–4472
51. Turino, G. M., Barker, A. F., Brantly, M. L., Cohen, A. B., Connelly, R. P., Crystal, R. G., … Stoller, J. K. (1996). Clinical features of individuals with PI*SZ phenotype of alpha 1-antitrypsin deficiency. alpha 1-Antitrypsin Deficiency Registry Study Group. American Journal of Respiratory and Critical Care Medicine, 154, 1718–1725
52. Wang, M., & Wei, L. (2016). iFish: Predicting the pathogenicity of human nonsynonymous variants using gene-specific/family-specific attributes and classifiers. Scientific Reports, 6, 31321