Genetic testing for Alpha1-antitrypsin deficiency

Strange, Charlie; Dickson, Ryan; Carter, Cindy; Carpenter, Matthew J.; Holladay, Brian; Lundquist, Ryan; Brantly, Mark

doi:10.1097/01.gim.0000132669.09819.79

Cited by 40 publications

(25 citation statements)

References 23 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[17][18][19] Offers for genetic testing made via the mail for alpha-1 antitrypsin deficiency, a smoking-linked form of emphysema, reported an uptake rate of 33%. 9,10 This rate is slightly lower than that found in the GSTM1 studies, but may be a useful comparison for the current study.…”

mentioning

confidence: 44%

“…For example, one trial delivered genetic susceptibility testing for alpha-1 antitrypsin deficiency, a smoking-linked form of emphysema, via the mail to unaffected individuals with some success. 9,10 Results of another trial, in which a computer-based decision-aid enhanced the knowledge of low-risk women with personal or family histories of breast cancer seeking BRCA1/2 susceptibility testing, suggest that such methods could potentially reduce the burden on genetic counselors who are limited in number in the United States and abroad. 11 The Internet may be another promising means to deliver genetic susceptibility testing information and services, though the authors of the above trials rightly caution that research on alternate delivery models is nascent.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The feasibility of online genetic testing for lung cancer susceptibility: uptake of a web-based protocol and decision outcomes

O’Neill

White

Sanderson

et al. 2008

Genetics in Medicine

View full text Add to dashboard Cite

Purpose: To examine the feasibility of offering genetic susceptibility testing for lung cancer (GSTM1) via the Internet to smokers who were blood relatives of patients with lung cancer. Outcomes include proportion who logged on to the study website to consider testing, made informed decisions to log on and to be tested. Methods: Baseline measures were assessed via telephone survey. Participants could choose to log on to the study website; those who did were offered testing. Informed decisions to log on and to be tested were indicated by concordance between the decision outcome and test-related attitudes and knowledge. Results: Three hundred four relatives completed baseline interviews. One hundred sixteen eligible relatives expressed further interest in receiving information via the web. Fifty-eight logged on and 44 tested. Those logging on expressed greater quit motivation, awareness of cancer genetic testing, and were more likely to be daily Internet users than those who did not log on. Approximately half of the sample made informed decisions to log on and to be tested. Conclusion: Interest in a web-based protocol for genetic susceptibility testing was high. Internet-delivered decision support was as likely as other modalities to yield informed decisions. Some subgroups may need additional support to improve their decision outcomes. Genet Med 2008:10(2):121-130. Key Words: Internet, genetic testing, test uptake, decision making, GSTM1, lung cancerAvailability of genetic susceptibility testing for common diseases is likely to increase as the evidence supporting gene-disease associations continues to grow. 1 There is a good deal of optimism that such testing might be beneficial for motivating individuals to adopt healthy lifestyles. 2 Genetic susceptibility testing for lung cancer has been suggested as a means to motivate smoking cessation. 3 However, a challenge for integrating such testing into smoking cessation or other behavior change interventions is that most of these interventions are self-directed, low intensity, and obliged to be low in cost to maximize dissemination. 4 Before any such integration, the feasibility of offering genetic susceptibility testing and conveying risk feedback, via alternate, user-friendly, self-directed delivery models, such as the Internet, must be assessed. 5 To our knowledge, no studies to date have offered genetic susceptibility testing using solely a web-based format. This is despite the fact that 75% of Americans use the Internet on a regular basis, and the impact of Internet applications on physician-patient communication and health care delivery continues to expand. 6 -8 Though no studies have examined delivery of genetic test results via the Internet, research to date supports the examination of alternate delivery models in some settings. For example, one trial delivered genetic susceptibility testing for alpha-1 antitrypsin deficiency, a smoking-linked form of emphysema, via the mail to unaffected individuals with some success. 9,10 Results of another trial, in which ...

show abstract

mentioning

confidence: 44%

mentioning

confidence: 99%

The feasibility of online genetic testing for lung cancer susceptibility: uptake of a web-based protocol and decision outcomes

O’Neill

White

Sanderson

et al. 2008

Genetics in Medicine

View full text Add to dashboard Cite

show abstract

“…This approach not only leads to the unambiguous identification of combinations of alleles responsible for ␣ 1 AT deficiency in index patients but also offers the possibility of a risk inventory for their families. This capability is beneficial because recent studies have demonstrated that significant positive effects are associated with the early identification of ␣ 1 AT-deficient individuals (36 ). Importantly, such effects would include an increased willingness to reduce exposure to environmental risk factors, such as cigarette smoking.…”

Section: Discussionmentioning

confidence: 99%

Inherited Chronic Obstructive Pulmonary Disease: New Selective-Sequencing Workup for α1-Antitrypsin Deficiency Identifies 2 Previously Unidentified Null Alleles

Prins¹,

Meijden

Kraaijenhagen

et al. 2008

Clinical Chemistry

View full text Add to dashboard Cite

Background: α1-Antitrypsin (α1AT) deficiency predisposes individuals to chronic obstructive pulmonary disease (COPD) and/or liver disease. Phenotyping of the protein by isoelectric focusing is often used to characterize α1AT deficiency, but this method may lead to misdiagnosis (e.g., by missing null alleles). We evaluated a workup that included direct sequencing of the relevant parts of the gene encoding α1AT, SERPINA1 [serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1], for patients with α1AT concentrations ≤1.0 g/L. Methods: During a 5-year period, we identified 66 patients with α1AT concentrations ≤1.0 g/L and amplified and sequenced exons 2, 3, and 5 of the α1AT gene in these patients. To ensure that no relevant genotypes were missed, we sequenced the same exons in 48 individuals with α1AT concentrations between 1.0 and 1.5 g/L. Results: Sequence analysis revealed 18 patients with combinations of disease-associated α1AT alleles: 8 homozygous for the deficient Z allele and 10 compound heterozygotes for various deficient or null alleles. We identified and named 2 new null alleles, Q0soest (Thr102→delA, which produces a TGA stop signal at codon 112) and Q0amersfoort (Tyr160→stop). No relevant disease-associated allele combinations were missed at a 1.0-g/L threshold. Conclusions: Up to 22% of the alleles in disease-associated α1AT allele combinations may be missed by conventional methods. Genotyping by direct sequencing of samples from patients with α1AT concentrations ≤1.0 g/L detected these alleles and identified 2 new null alleles.

show abstract

“…Еще одной причиной гибели пациентов с дефицитом А1АТ являются онколо-гические заболевания. Для данной группы пациентов характерно развитие рака печени без предшествующе-го предракового состояния [30,31]. У пациентов с PiZ-аллелью холангиокарциномы, гепатохолангиокарциномы встречаются чаще, чем в общей популяции [4].…”

Section: Discussionunclassified