Applying a multiplexed primer extension method on dried blood spots increased the detection of carriers at risk of glucose-6-phosphate dehydrogenase deficiency in newborn screening program

Yen Hui Chiu, Hsiao Jan Chen, Ying Chen Chang, Yu Ning Liu, Shu Min Kao, Mei Ying Liu, Ying Yen Weng, Kwang Jen Hsiao, Tze Tze Liu*

*此作品的通信作者

研究成果: Article同行評審

11 引文 斯高帕斯(Scopus)

摘要

Background: Patients with glucose-6-phosphate dehydrogenase deficiency might develop acute hemolytic anemia, chronic hemolytic anemia, and neonatal hyperbilirubinemia when exposed to high levels of oxidative stress. Severe hemolysis may occur in not only patients but also female carriers under certain conditions. However, 80%–85% of female carriers were undetected in an existing newborn screening program because of their wide-ranging levels of enzyme activity. Methods: We developed a cost- and time-efficient multiplex SNaPshot assay using dried blood spots. Results: By detecting 21 common mutations in Taiwan and Southeast Asia, the assay could determine 98.2% of the mutant alleles in our cohort of Taiwanese newborns. The 9 undetermined mutant alleles were consequently detected by Sanger sequencing, of which 5 unpublished variations—c.187G > A (Pingtung), c.585G > C (Tainan), c.586A > T (Changhua), c.743G > A (Chiayi), and c.1330G > A (Tainan-2)—were detected. Furthermore, 13% of mild mutations were missed in male infants whose enzyme levels at 6.1–7.0 U/gHb in the newborn screening program when set the cutoff value at 6.0 U/gHb. We therefore suggest increasing the cutoff value and applying the multiplex SNaPshot assay as the second tier for neonatal screening. Conclusions: Our approach could significantly increase the detection rate of male patients and female carriers with a reasonable cost and a reasonable number of clinic referrals.

原文English
頁(從 - 到)271-277
頁數7
期刊Clinica Chimica Acta
495
DOIs
出版狀態Published - 8月 2019

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