Zorzetto Michele, Ferrarotti Ilaria, Campo Ilaria, Balestrino Antonella, Nava Stefano, Gorrini Marina, Scabini Roberta, Mazzola Paola, Luisetti Maurizio
Clinica Malattie Apparato Respiratorio, IRCCS Policlinico S. Matteo, Pavia 27100, Italy.
Diagn Mol Pathol. 2005 Jun;14(2):121-4. doi: 10.1097/01.pas.0000155023.74859.d6.
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, PIZ and PIS. 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.
α1-抗胰蛋白酶缺乏症（AATD）是一种常见的遗传性疾病，与早年发生肺气肿的高风险相关，在较小程度上还与慢性肝病和肝硬化有关。在北欧人和北美人中，超过95%患有与AATD相关的肺气肿的个体携带最常见的AAT缺陷基因变体PIZ和PIS。罕见的AAT缺陷变体占AATD个体的2 - 4%。我们通过对在3名受试者中检测到的一种新型无效等位基因进行特征分析，扩展了AAT的序列数据：一名属于意大利/埃及家庭的携带者以及一名来自意大利南部家庭的2名成员。该突变发生在一个M1（Ala213）碱基等位基因上，其特征是外显子III第218位核苷酸、密码子259（AAA→TAA）处发生A→T颠换（基因库登录号AY 256958）。这种颠换导致一个提前的终止密码子（Lys259AAA→Stop259TAA）。提议的命名Q0cairo来自首个被确认受试者父亲的出生地。AAT的血清水平和等电聚焦与无效变体的存在一致。
