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Prevalence and phenotype of subjects carrying rare variants in the Italian registry for alpha1-antitrypsin deficiency
  1. I Ferrarotti1,
  2. J Baccheschi1,
  3. M Zorzetto1,
  4. C Tinelli2,
  5. L Corda3,
  6. B Balbi4,
  7. I Campo1,
  8. E Pozzi1,
  9. G Faa5,
  10. P Coni5,
  11. G Massi6,
  12. G Stella1,
  13. M Luisetti1
  1. 1Centro di Diagnosi e di Coordinamento del Registro Italiano per il Deficit Severo di Alfa1-antitripsina, Laboratorio di Biochimica e Genetica, Clinica di Malattie dell’Apparato Respiratorio, Pavia, Italy
  2. 2Servizio di Biometria ed Epidemiologia Clinica, IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy
  3. 3I Divisione di Medicina, Spedali Civili, Università di Brescia, Brescia, Italy
  4. 4Divisione di Pneumologia, Fondazione S Maugeri, Gussago (BS), Italy
  5. 5Dipartimento di Citomorfologia, Università di Cagliari, Cagliari, Italy
  6. 6Laboratorio per la Diagnosi del Deficit Congenito di Alfa1-antitripsina, Università Cattolica del Sacro Cuore, Rome, Italy
  1. Correspondence to:
 Dr Maurizio Luisetti
 Clinica di Malattie dell’Apparato Respiratorio, IRCCS Policlinico San Matteo, Università di Pavia, via Taramelli 5, 27100 Pavia, Italy; m.luisettismatteo.pv.it

https://doi.org/10.1136/jmg.2004.023903

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    Alpha1-antitrypsin deficiency (AATD) is a genetic condition associated with an increased risk of developing chronic obstructive pulmonary disease (COPD) early in life and, to a lesser extent, liver disease.1 Significant advances have been made during the last decades in understanding its epidemiology and it has been recently suggested that AATD is one of the commonest inherited disorders not only in Caucasians but also among other ethnic groups worldwide.2,3

    Although AAT is a highly pleomorphic glycoprotein, with approximately 100 variants having being identified,4 two major deficient variants, namely Z and S, account for most cases of AATD, since the vast majority of such individuals carry the PI*ZZ or PI*SZ genotype, coding for approximately 15% and 25%, respectively, of normal AAT plasma levels. The establishment of international registries, including large series of AATD individuals,5,6 has allowed not only better definition of the epidemiology of AATD, but also more precise definition of the associated clinical phenotypes.5,7,8

    Nevertheless, there are at least 30 AAT alleles other than the PI*Z and the PI*S alleles which are associated with significantly reduced or absent plasma AAT levels.9 Given the extreme rarity of such variants, often described in the literature as single case reports, little is known about their epidemiology and even less is known about the associated clinical phenotypes.

    The Italian Registry for Severe AATD was established in 1996 as a result of a nationwide screening programme sponsored by the two major Italian scientific respiratory societies.10 Although Italy is considered a country with a medium-low prevalence of AATD (mean PI*Z gene frequency: 0.0013),11 the programme succeeded in identifying a relatively large cohort of AATD individuals. During the development of the screening program, we noticed that, in addition to the groups of AATD individuals …

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