Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency.
Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency.
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DOI：
10.1177/20406223211015954
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发表时间：
2021
影响因子：
3.5
通讯作者：
Foil KE
中科院分区：
文献类型：
--
作者：
Foil KE
α -1抗胰蛋白酶缺乏症（AATD）是由编码α -1抗胰蛋白酶（AAT）蛋白的SERPINA1基因突变引起的。目前，已经鉴定出200多种SERPINA1变异，其中许多变异导致AAT的定量和/或定性变化，导致aatd相关的肺和肝脏疾病。这些致病突变的类型多种多样，通常导致AAT氨基酸序列的错误折叠或截断，测序技术的改进有助于识别已知和新的遗传变异。然而，由于罕见变异的多样性和新颖性，许多的临床意义在很大程度上是未知的。因此，当患者的变异组合的临床意义不明确或不确定时，缺乏对患者应如何监测和治疗的指导。然而，重要的是医生要了解诊断AATD的不同测试方法的优缺点。由于导致AATD的基因突变具有常染色体遗传，因此不仅应该对AATD风险增加的患者（如慢性阻塞性肺疾病患者）进行基因检测，而且应该对结果异常的患者的亲属进行基因检测。遗传咨询可以帮助患者和家庭成员了解检测的可能结果和对家庭的影响。虽然基因诊断或确认携带者身份可能导致压力/焦虑，但基因检测也可能产生积极后果，包括改善生活方式的选择、有针对性的医疗护理和增强计划生育能力。随着基因检测技术的发展和普及，没有医生推荐的检测变得越来越普遍，无论是否有遗传咨询。因此，Alpha-1基金会为AATD患者及其家人和医生提供遗传咨询，以及其他支持和教育材料，以帮助提高对基因检测潜在益处和后果的理解。
Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in the SERPINA1 gene, which encodes the alpha-1 antitrypsin (AAT) protein. Currently, over 200 SERPINA1 variants have been identified, many of which cause the quantitative and/or qualitative changes in AAT responsible for AATD-associated lung and liver disease. The types of these pathogenic mutations are varied, often resulting in misfolding, or truncating of the AAT amino acid sequence, and improvements in sequencing technology are helping to identify known and novel genetic variants. However, due to the diversity and novelty of rare variants, the clinical significance of many is largely unknown. There is, therefore, a lack of guidance on how patients should be monitored and treated when the clinical significance of their variant combination is unclear or variable. Nevertheless, it is important that physicians understand the advantages and disadvantages of the different testing methodologies available to diagnose AATD. Owing to the autosomal inheritance of the genetic mutations responsible for AATD, genetic testing should be offered not only to patients at increased AATD risk (e.g. patients with chronic obstructive pulmonary disease), but also to relatives of those with an abnormal result. Genetic counseling may help patients and family members understand the possible outcomes of testing and the implications for the family. While stress/anxiety can arise from genetic diagnosis or confirmation of carrier status, there can be positive consequences to genetic testing, including improved lifestyle choices, directed medical care, and empowered family planning. As genetic testing technology grows and becomes more popular, testing without physician referral is becoming more prevalent, irrespective of the availability of genetic counseling. Therefore, the Alpha-1 Foundation offers genetic counseling, as well as other support and educational material, for patients with AATD, as well as their families and physicians, to help improve the understanding of potential benefits and consequences of genetic testing.
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影响因子：
24.3
作者：
Costa, X;Jardi, R;Vidal, R
通讯作者：
Vidal, R
DOI：
10.1164/ajrccm/137.2.371
发表时间：
1988-02-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
COX, DW;LEVISON, H
通讯作者：
LEVISON, H
影响因子：
9.6
作者：
Eriksson, S
通讯作者：
Eriksson, S
影响因子：
15.9
作者：
CRYSTAL, RG
通讯作者：
CRYSTAL, RG
DOI：
10.1016/0167-4838(86)90183-4
发表时间：
1986-09-05
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
BRENNAN, SO;CARRELL, RW
通讯作者：
CARRELL, RW