Detection of common sequence variations of familial hypercholesterolemia in Taiwan using DNA mass spectrometry

Kuan Rau Chiou, Min Ji Charng

研究成果: 雜誌貢獻 › 文章

3 引文 (Scopus)

摘要

Background Familial hypercholesterolemia (FH) is a heterogeneous autosomal dominant disease. The genetic heterogeneity of FH requires low-cost, high-throughput, and rapid mutation detection technology to efficiently integrate genetic screening into clinical practice. Objectives The aims of the study were to customize the MassARRAY assay to (1) establish an FH mutation assay panel, comprising known point mutations located on FH-causing genes and (2) test the feasibility of the assay for screening FH patients residing in Taiwan who fit the clinical criteria of FH diagnosis. Methods We designed a custom Agena iPLEX assay to detect 68 point mutations on FH-causing genes. First, the assay performance was verified by analyzing 180 previously sequenced subjects (120 with point mutations and 60 healthy controls), with the results being compared with those of Sanger DNA sequencing. Second, a blind study was carried out on 185 FH probands (44 definite FH and 141 probable/possible FH). Results In the first part of this study, only 1 discrepancy was found between the Agena iPLEX and Sanger sequencing genotyping results. In the blind study, a total of 62 probands with mutations were identified by both techniques. Five mutations were detected by Sanger sequencing assay only. The detection sensitivity and specificity rates of Agena iPLEX were 92.5% and 100%, respectively, in the blind study. The hands-on time for the Agena iPLEX assay was around 1 day. Conclusions The custom-designed Agena iPLEX assay has high specificity and sensitivity for FH genetic screening. Considering its low cost, rapidity, and flexibility, the assay has great potential to be incorporated into FH screening in Taiwan.
原文英語
頁（從 - 到）386-393.e6
期刊Journal of Clinical Lipidology
卷11
發行號2
DOIs
出版狀態已發佈 - 三月 1 2017
對外發佈Yes

指紋

Hyperlipoproteinemia Type II
Taiwan
Mass Spectrometry
DNA
Point Mutation
Mutation
Genetic Testing
Costs and Cost Analysis
Sensitivity and Specificity
Genetic Heterogeneity
DNA Sequence Analysis
Genes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

引用此文

Detection of common sequence variations of familial hypercholesterolemia in Taiwan using DNA mass spectrometry. / Chiou, Kuan Rau; Charng, Min Ji.

於: Journal of Clinical Lipidology, 卷 11, 編號 2, 01.03.2017, p. 386-393.e6.

研究成果: 雜誌貢獻 › 文章

Chiou, KR & Charng, MJ 2017, 'Detection of common sequence variations of familial hypercholesterolemia in Taiwan using DNA mass spectrometry', Journal of Clinical Lipidology, 卷 11, 編號 2, 頁 386-393.e6. https://doi.org/10.1016/j.jacl.2016.12.014
Chiou KR, Charng MJ. Detection of common sequence variations of familial hypercholesterolemia in Taiwan using DNA mass spectrometry. Journal of Clinical Lipidology. 2017 3月 1;11(2):386-393.e6. https://doi.org/10.1016/j.jacl.2016.12.014
Chiou, Kuan Rau ; Charng, Min Ji. / Detection of common sequence variations of familial hypercholesterolemia in Taiwan using DNA mass spectrometry. 於: Journal of Clinical Lipidology. 2017 ; 卷 11, 編號 2. 頁 386-393.e6.
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abstract = "Background Familial hypercholesterolemia (FH) is a heterogeneous autosomal dominant disease. The genetic heterogeneity of FH requires low-cost, high-throughput, and rapid mutation detection technology to efficiently integrate genetic screening into clinical practice. Objectives The aims of the study were to customize the MassARRAY assay to (1) establish an FH mutation assay panel, comprising known point mutations located on FH-causing genes and (2) test the feasibility of the assay for screening FH patients residing in Taiwan who fit the clinical criteria of FH diagnosis. Methods We designed a custom Agena iPLEX assay to detect 68 point mutations on FH-causing genes. First, the assay performance was verified by analyzing 180 previously sequenced subjects (120 with point mutations and 60 healthy controls), with the results being compared with those of Sanger DNA sequencing. Second, a blind study was carried out on 185 FH probands (44 definite FH and 141 probable/possible FH). Results In the first part of this study, only 1 discrepancy was found between the Agena iPLEX and Sanger sequencing genotyping results. In the blind study, a total of 62 probands with mutations were identified by both techniques. Five mutations were detected by Sanger sequencing assay only. The detection sensitivity and specificity rates of Agena iPLEX were 92.5{\%} and 100{\%}, respectively, in the blind study. The hands-on time for the Agena iPLEX assay was around 1 day. Conclusions The custom-designed Agena iPLEX assay has high specificity and sensitivity for FH genetic screening. Considering its low cost, rapidity, and flexibility, the assay has great potential to be incorporated into FH screening in Taiwan.",
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N2 - Background Familial hypercholesterolemia (FH) is a heterogeneous autosomal dominant disease. The genetic heterogeneity of FH requires low-cost, high-throughput, and rapid mutation detection technology to efficiently integrate genetic screening into clinical practice. Objectives The aims of the study were to customize the MassARRAY assay to (1) establish an FH mutation assay panel, comprising known point mutations located on FH-causing genes and (2) test the feasibility of the assay for screening FH patients residing in Taiwan who fit the clinical criteria of FH diagnosis. Methods We designed a custom Agena iPLEX assay to detect 68 point mutations on FH-causing genes. First, the assay performance was verified by analyzing 180 previously sequenced subjects (120 with point mutations and 60 healthy controls), with the results being compared with those of Sanger DNA sequencing. Second, a blind study was carried out on 185 FH probands (44 definite FH and 141 probable/possible FH). Results In the first part of this study, only 1 discrepancy was found between the Agena iPLEX and Sanger sequencing genotyping results. In the blind study, a total of 62 probands with mutations were identified by both techniques. Five mutations were detected by Sanger sequencing assay only. The detection sensitivity and specificity rates of Agena iPLEX were 92.5% and 100%, respectively, in the blind study. The hands-on time for the Agena iPLEX assay was around 1 day. Conclusions The custom-designed Agena iPLEX assay has high specificity and sensitivity for FH genetic screening. Considering its low cost, rapidity, and flexibility, the assay has great potential to be incorporated into FH screening in Taiwan.

AB - Background Familial hypercholesterolemia (FH) is a heterogeneous autosomal dominant disease. The genetic heterogeneity of FH requires low-cost, high-throughput, and rapid mutation detection technology to efficiently integrate genetic screening into clinical practice. Objectives The aims of the study were to customize the MassARRAY assay to (1) establish an FH mutation assay panel, comprising known point mutations located on FH-causing genes and (2) test the feasibility of the assay for screening FH patients residing in Taiwan who fit the clinical criteria of FH diagnosis. Methods We designed a custom Agena iPLEX assay to detect 68 point mutations on FH-causing genes. First, the assay performance was verified by analyzing 180 previously sequenced subjects (120 with point mutations and 60 healthy controls), with the results being compared with those of Sanger DNA sequencing. Second, a blind study was carried out on 185 FH probands (44 definite FH and 141 probable/possible FH). Results In the first part of this study, only 1 discrepancy was found between the Agena iPLEX and Sanger sequencing genotyping results. In the blind study, a total of 62 probands with mutations were identified by both techniques. Five mutations were detected by Sanger sequencing assay only. The detection sensitivity and specificity rates of Agena iPLEX were 92.5% and 100%, respectively, in the blind study. The hands-on time for the Agena iPLEX assay was around 1 day. Conclusions The custom-designed Agena iPLEX assay has high specificity and sensitivity for FH genetic screening. Considering its low cost, rapidity, and flexibility, the assay has great potential to be incorporated into FH screening in Taiwan.

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