Genetic diagnosis of α1-antitrypsin deficiency using DNA from buccal swab and serum samples

Belmonte, Irene; Barrecheguren, Miriam; Esquinas, Cristina; Rodrı́guez, Esther; Miravitlles, Marc; Rodríguez‐Frías, Francisco

doi:10.1515/cclm-2016-0842

Cited by 6 publications

(5 citation statements)

References 30 publications

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“…However, mainly due to some limitations comprising the invasiveness and the costs of blood sample management, clinicians have long searched for alternative sources of DNA. Oral samples consisting of dry buccal swabs or wet saliva collections are valid alternative sources of germline DNA, and a limited number of blood and buccal swab comparison studies across different genotyping platforms is available 9–13. Meghnani et al demonstrated the suitability of buccal swabs in a study concerning BRCA genotyping performed using the Ion Torrent system 12.…”

Section: Resultsmentioning

confidence: 99%

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BRCAtesting on buccal swab to improve access to healthcare and cancer prevention: a performance evaluation

Paolis

Perrucci

Marchetti

et al. 2022

Int J Gynecol Cancer

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ObjectiveBRCA1/2 (BRCA) genetic testing allows patients with high-grade serous ovarian cancer to receive appropriate medical management with molecular target therapy and prevention strategies. Most of the BRCA sequencing methods use blood as the primary source of germline DNA. Buccal swab emerged as an alternative collection device due to its convenient and non-invasive characteristics. This study assessed the suitability of buccal swabs as the DNA source in next-generation sequencing-based BRCA genotyping.MethodsMatched buccal swabs and blood samples were collected from 51 patients with high-grade serous ovarian cancer, including 29 BRCA-mutated patients, from June to December 2021. Buccal swabs were self-collected using COPAN FLOQSwabs hDNA Free. BRCA genes were amplified using Devyser’s BRCA next-generation sequencing kit and sequenced on the Illumina MiSeq platform. We evaluated collection and extraction procedures, amplification and sequencing performances, coverage data, blood/swab variant calling concordance, and interpretation.ResultsComparable sequencing parameters were observed between the two sample types in term of mean total number of reads passing filter for indexed sample (p>0.05) and sequencing coverage distribution, with a widespread overlap of mean depth of coverage/target region between blood and swab samples. An overall concordance of 100% in both polymorphisms and pathogenic variants calling between the two DNA sources were observed, including the copy number variation prediction.ConclusionsData from this study support the use of buccal swabs as an alternative source of DNA for BRCA evaluation. The use of this alternative delivery mode of BRCA testing may facilitate access to care without compromising patient outcomes.

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Section: Resultsmentioning

confidence: 99%

“…Currently, there is a limited number of blood and buccal swab comparison studies available in the literature 9–13. Here, we evaluated the suitability of buccal swabs as a DNA source in our BRCA next-generation sequencing pipeline.…”

Section: Introductionmentioning

confidence: 99%

BRCAtesting on buccal swab to improve access to healthcare and cancer prevention: a performance evaluation

Paolis

Perrucci

Marchetti

et al. 2022

Int J Gynecol Cancer

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“…Serum, plasma, whole blood or buccal swap samples were used indifferently for genotyping methods. 16 …”

Section: Methodsmentioning

confidence: 99%

“…Serum, plasma, whole blood or buccal swap samples were used indifferently for genotyping methods. 16 Data about request origin and the reason for the request for AAT determination were collected, when available. Since one of the main consequences of AATD is liver disease, we also tested some biochemical markers of liver damage available in routine blood analysis, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and calculated the Fibrosis-4 (FIB-4) score as (patient age x AST (IU/L))/(platelet count (x10 9 /L) x ALT −1/2 (IU/L)).…”

Section: Selection Of Samplesmentioning

confidence: 99%

<p>Trends in Diagnosis of Alpha-1 Antitrypsin Deficiency Between 2015 and 2019 in a Reference Laboratory</p>

Belmonte

Núñez

Barrecheguren

et al. 2020

COPD

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Background: Alpha-1 antitrypsin deficiency (AATD) remains largely underdiagnosed despite recommendations of healthcare institutions and programmes designed to increase awareness. The objective was to analyse the trends in AATD diagnosis during the last 5 years in a Spanish AATD reference laboratory. Methods: This was a retrospective revision of all alpha-1 antitrypsin (AAT) determinations undertaken in our laboratory from 2015 to 2019. We analysed the number of AAT determinations performed and described the characteristics of the individuals tested, as well as the medical specialties and the reasons for requesting AAT determination. Results: A total of 3507 determinations were performed, of which 5.5% corresponded to children. A significant increase in the number of AAT determinations was observed from 349 in 2015 to 872 in 2019. Among the samples, 57.6% carried an intermediate AATD (50-119 mg/dL) and 2.4% severe deficiency (<50 mg/dL). The most frequent phenotype in severe AATD individuals was PI*ZZ (78.5%), and aminotransferase levels were above normal in around 43% of children and 30% of adults. Respiratory specialists requested the highest number of AAT determinations (31.5%) followed by digestive diseases and internal medicine (27.5%) and primary care physicians (19.7%). The main reason for AAT determination in severe AATD adults was chronic obstructive pulmonary disease (41.7%), but reasons for requesting AAT determination were not reported in up to 41.7% of adults and 58.3% of children. Conclusion: There is an increase in the frequency of AATD testing despite the rate of AAT determination remaining low. Awareness about AAT is probably increasing, but the reason for testing is not always clear.

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“… 55 In practice, AATD testing consists of at least one of four fundamental steps: determination of AAT serum levels, IEF phenotyping, allele-specific genotyping, and direct sequencing. 56 Measurement of AAT serum levels can detect some, but not all severe AAT deficiencies. When serum levels are severely low, additional testing is required for comprehensive diagnosis and risk assessment.…”

Section: Testingmentioning

confidence: 99%

Variants ofSERPINA1and the increasing complexity of testing for alpha-1 antitrypsin deficiency

Foil

2021

Therapeutic Advances in Chronic Disease

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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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Genetic diagnosis of α1-antitrypsin deficiency using DNA from buccal swab and serum samples

Cited by 6 publications

References 30 publications

BRCAtesting on buccal swab to improve access to healthcare and cancer prevention: a performance evaluation

BRCAtesting on buccal swab to improve access to healthcare and cancer prevention: a performance evaluation

<p>Trends in Diagnosis of Alpha-1 Antitrypsin Deficiency Between 2015 and 2019 in a Reference Laboratory</p>

Variants ofSERPINA1and the increasing complexity of testing for alpha-1 antitrypsin deficiency

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