Type

Journal Article

Authors

Maurizio Luisetti
Noel G McElvaney
David R Curran
Daniela Medicina
Luciano Corda
Kevin Molloy
Geraldine O'Brien
Anna M Fra
Stefania Ottaviani
Tomás P Carroll
and 1 others

Subjects

Veterinary

Topics
diagnosis detection lung diseases characterisation liver disease isoelectric focusing alpha 1 antitrypsin blood

Identification and characterisation of eight novel SERPINA1 Null mutations. (2014)

Abstract Alpha-1 antitrypsin (AAT) is the most abundant circulating antiprotease and is a member of the serine protease inhibitor (SERPIN) superfamily. The gene encoding AAT is the highly polymorphic SERPINA1 gene, found at 14q32.1. Mutations in the SERPINA1 gene can lead to AAT deficiency (AATD) which is associated with a substantially increased risk of lung and liver disease. The most common pathogenic AAT variant is Z (Glu342Lys) which causes AAT to misfold and polymerise within hepatocytes and other AAT-producing cells. A group of rare mutations causing AATD, termed Null or Q0, are characterised by a complete absence of AAT in the plasma. While ultra rare, these mutations confer a particularly high risk of emphysema. We performed the determination of AAT serum levels by a rate immune nephelometric method or by immune turbidimetry. The phenotype was determined by isoelectric focusing analysis on agarose gel with specific immunological detection. DNA was isolated from whole peripheral blood or dried blood spot (DBS) samples using a commercial extraction kit. The new mutations were identified by sequencing all coding exons (II-V) of the SERPINA1 gene. We have found eight previously unidentified SERPINA1 Null mutations, named: Q0cork, Q0perugia, Q0brescia, Q0torino, Q0cosenza, Q0pordenone, Q0lampedusa, and Q0dublin . Analysis of clinical characteristics revealed evidence of the recurrence of lung symptoms (dyspnoea, cough) and lung diseases (emphysema, asthma, chronic bronchitis) in M/Null subjects, over 45 years-old, irrespective of smoking. We have added eight more mutations to the list of SERPINA1 Null alleles. This study underlines that the laboratory diagnosis of AATD is not just a matter of degree, because the precise determination of the deficiency and Null alleles carried by an AATD individual may help to evaluate the risk for the lung disease.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Maurizio Luisetti, Noel G McElvaney, David R Curran, Daniela Medicina, Luciano Corda, Kevin Molloy, Geraldine O'Brien, Anna M Fra, Stefania Ottaviani, Tomás P Carroll and 1 others

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Kevin Molloy
Royal College of Surgeons in Ireland
Total Publications: 19
 
3
Tomás P Carroll
Royal College of Surgeons in Ireland
Total Publications: 26