title: Identification of a novel alpha1-antitrypsin null variant (Q0Cairo).
abstract: Alpha1-antitrypsin deficiency (AATD) is a common hereditary disorder associated with high risk of developing pulmonary emphysema early in life and, to a lesser extent, chronic liver disease and cirrhosis. Among Northern Europeans and Northern Americans, more than 95% of individuals with emphysema associated with AATD carry the most frequent AAT deficient gene variants, PI*Z and PI*S. Rare AAT deficient variants account for 2-4% of AATD individuals. We extend the sequence data on AAT by characterizing a novel Null allele detected in 3 subjects: a carrier belonging to an Italian/Egyptian family and 2 members of a family originating from Southern Italy. The mutation raised on a M1 (Ala213) base allele and it is characterized by an A-->T transversion at exon III, nt 218, codon 259 (AAA-->TAA) (GeneBank accession number AY 256958). The transversion results in a premature stop codon (Lys259AAA-->Stop259TAA). The proposed nomenclature of Q0cairo is from the birthplace of the father of first recognized subject. Serum levels and isoelectric focusing of AAT were consistent with the presence of the Null variant.
authors.affiliation: Clinica Malattie Apparato Respiratorio, IRCCS Policlinico S. Matteo, Pavia 27100, Italy. m.zorzetto@smatteo.pv.it
authors.forename: Michele
authors.initials: M
authors.lastname: Zorzetto
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrarotti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Campo
authors.forename: Antonella
authors.initials: A
authors.lastname: Balestrino
authors.forename: Stefano
authors.initials: S
authors.lastname: Nava
authors.forename: Marina
authors.initials: M
authors.lastname: Gorrini
authors.forename: Roberta
authors.initials: R
authors.lastname: Scabini
authors.forename: Paola
authors.initials: P
authors.lastname: Mazzola
authors.forename: Maurizio
authors.initials: M
authors.lastname: Luisetti
mesh_terms: D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics*
chemical_list: D000515:alpha 1-Antitrypsin