Carpagnano G E, Santacroce R, Palmiotti G A, Leccese A, Giuffreda E, Margaglione M, Foschino Barbaro M P, Aliberti S, Lacedonia D
Department of Medical and Surgical Sciences, Institute of Respiratory Diseases, University of Foggia, Foggia, Italy.
Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Lung. 2017 Oct;195(5):679-682. doi: 10.1007/s00408-017-0033-2. Epub 2017 Jul 1.
Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We report a case of a 52-year-old woman with bronchiectasis without other potential causes other than an electrophoresis that showed a decrease of alpha-1 globin band and AAT levels below the normal value (78 mg/dl; v.n. 90-200 mg/dl). No S or Z mutation was identified, but sequencing analysis found a novel missense variant Ile74Asn (c.221T > A) in heterozygous state on an M3 allele (Glu400Asp) in the exon 2 of the SERPINA-1gene, probably leading to a dysfunctional protein. This mutation has never been previously identified, and it is interesting to note the association with bronchiectasis in the absence of emphysema.
α-1抗胰蛋白酶缺乏症（AATD）是一种由SERPINA1基因突变引起的遗传疾病，最终导致血清中蛋白酶抑制剂活性降低，并易患肺气肿。AATD的临床表现通常与ZZ（p.Glu342Lys）和SZ（p.Glu264Val）基因型相关，而在杂合子和纯合子状态下，与罕见的缺乏或无效等位基因相关的情况较少见。我们报告了一例52岁女性支气管扩张症患者，除电泳显示α-1球蛋白带减少且AAT水平低于正常值（78mg/dl；正常范围90-200mg/dl）外，无其他潜在病因。未发现S或Z突变，但测序分析在SERPINA-1基因外显子2的M3等位基因（Glu400Asp）上发现了一个杂合状态的新型错义变体Ile74Asn（c.221T>A），可能导致蛋白质功能失调。该突变以前从未被发现，有趣的是，在没有肺气肿的情况下，它与支气管扩张症有关。
