High-throughput detection of common sequence variations of Fabry disease in Taiwan using DNA mass spectrometry

Lee, Sheng-Hung; Li, Chengfang; Lin, Hsiang‐Yu; Lin, Chang‐Yu; Liu, Hao-Chuan; Tsai, Shih‐Feng; Niu, Dau‐Ming

doi:10.1016/j.ymgme.2014.02.004

Cited by 15 publications

(12 citation statements)

References 31 publications

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“…DNA was isolated from whole blood using the GFX genomic Blood DNA Purification Kit (Amersham Biosciences, UK) following the manufacturer’s instructions. The primer sets were used to amplify the sequences of seven GLA exons and the region including IVS4 + 919G > A [24,25]. The polymerase chain reaction products were analyzed by 1.5% agarose I (Amresco) gel electrophoresis and then eluted in the polymerase chain reaction Advanced PCR Clean Up System (Viogene, USA.).…”

Section: Methodsmentioning

confidence: 99%

Endomyocardial biopsies in patients with left ventricular hypertrophy and a common Chinese later-onset fabry mutation (IVS4 + 919G > A)

Hsu

Sung

Chang

et al. 2014

Orphanet J Rare Dis

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BackgroundIn Taiwan, DNA-based newborn screening showed a surprisingly high incidence of a cardiac Fabry mutation (IVS4 + 919G > A). The prevalence of this mutation is too high to be believed that it is a real pathogenic mutation. The purpose of this study is to identify the cardiac pathologic characteristics in patients with left ventricular hypertrophy and this mutationMethods and resultsEndomyocardial biopsies were obtained in 22 patients (Median age: 61, males: 17; females: 5) with left ventricular hypertrophy and the IVS4 + 919G > A mutation; five patients had not received enzyme replacement therapy (ERT) before biopsy, while the other 17 patients had received ERT from 8 months to 51 months. Except for three patients who had received ERT for more than 3 years, all other patients showed significant pathological change and globotriaosylceramide (Gb3) accumulation in their cardiomyocytes. In contrast to classical Fabry patients, no Gb3 accumulation was found in the capillary endothelial cells of any of our patients. Fourteen patients (63.6%) were found to have myofibrillolysis.ConclusionsAll of the untreated and most of the treated IVS4 + 919G > A patients showed typical pathological changes of Fabry disease in their cardiomyocytes. No endothelial accumulation of Gb3 was found, which is similar to the findings of several previous reports regarding later-onset Fabry disease. This result highly suggests that the IVS4 + 919G > A is a real pathogenic later-onset Fabry mutation.

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Section: Methodsmentioning

confidence: 99%

Endomyocardial biopsies in patients with left ventricular hypertrophy and a common Chinese later-onset fabry mutation (IVS4 + 919G > A)

Hsu

Sung

Chang

et al. 2014

Orphanet J Rare Dis

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“…Recently, genetic screening has been developed for the high‐risk population in both male and female patients . A Sequenom iPLEX assay has been designed and validated to identify α‐galactosidase A ( GLA ) gene mutations and variants with 100% accuracy and sensitivity in Taiwan .…”

Section: Introductionmentioning

confidence: 99%

Genomic screening of Fabry disease in young stroke patients: the Taiwan experience and a review of the literature

Lee

Yang

Lee

et al. 2018

Euro J of Neurology

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“…Left ventricular hypertrophy (LVH), the most common presentation of FC as a result of the progressive intracellular accumulation of globotriaosylceramide (Gb3), is potentially alleviated by early enzyme replacement therapy (ERT) with GLA [ 4 ]. For the populations of Fabry cohorts in Taiwan, a majority of Fabry patients have been identified to carry GLA IVS4+919 G>A mutation and late-onset cardiac phenotype at high incidence [ 5 , 6 , 7 , 8 , 9 , 10 ]. Clinical trials have demonstrated that ERT can reduce the risk of major clinical events, remodel the left ventricle, improve cardiac function, and increase exercise tolerance [ 11 ] However, disease progression still occurs in a minority of FC patients, particularly those with myocardial fibrosis after ERT [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Mass spectrometry-based proteomics is an effective approach for performing global investigations of proteome profiles in stem cell biology and cardiovascular research [ 6 , 7 , 22 , 23 ]. Previous research has used Fabry disease-derived plasma or urine samples for proteomic analysis and identification of new markers of Fabry disease [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Arachidonate 12/15-Lipoxygenase Improves α-Galactosidase Efficacy in iPSC-Derived Cardiomyocytes from Fabry Patients

Chien

Chou²,

Chang

et al. 2018

IJMS

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(1) Background: A high incidence of intervening sequence (IVS)4+919 G>A mutation with later-onset cardiac phenotype have been reported in a majority of Taiwan Fabry cohorts. Some evidence indicated that conventional biomarkers failed to predict the long-term progression and therapeutic outcome; (2) Methods: In this study, we constructed an induced pluripotent stem cell (iPSC)-based platform from Fabry cardiomyopathy (FC) patients carrying IVS4+919 G>A mutation to screen for potential targets that may help the conventional treatment; (3) Results: The FC-patient-derived iPSC-differentiated cardiomyocytes (FC-iPSC-CMs) carried an expected IVS4+919 G>A genetic mutation and recapitulated several FC characteristics, including low α-galactosidase A enzyme activity and cellular hypertrophy. The proteomic analysis revealed that arachidonate 12/15-lipoxygenase (Alox12/15) was the most highly upregulated marker in FC-iPSC-CMs, and the metabolites of Alox12/15, 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE), were also elevated in the culture media. Late administration of Alox12/15 pharmacological inhibitor LOXBlock-1 combined with α-galactosidase, but not α-galactosidase alone, effectively reduced cardiomyocyte hypertrophy, the secretion of 12(S)- and 15(S)-HETE and the upregulation of fibrotic markers at the late phase of FC; (4) Conclusions: Our study demonstrates that cardiac Alox12/15 and circulating 12(S)-HETE/15(S)-HETE are involved in the pathogenesis of FC with IVS4+919 G>A mutation.

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High-throughput detection of common sequence variations of Fabry disease in Taiwan using DNA mass spectrometry

Cited by 15 publications

References 31 publications

Endomyocardial biopsies in patients with left ventricular hypertrophy and a common Chinese later-onset fabry mutation (IVS4 + 919G > A)

Endomyocardial biopsies in patients with left ventricular hypertrophy and a common Chinese later-onset fabry mutation (IVS4 + 919G > A)

Genomic screening of Fabry disease in young stroke patients: the Taiwan experience and a review of the literature

Inhibition of Arachidonate 12/15-Lipoxygenase Improves α-Galactosidase Efficacy in iPSC-Derived Cardiomyocytes from Fabry Patients

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