A pilot study of expanded newborn screening for 573 genes related to severe inherited disorders in China: results from 1,127 newborns
Пилотное исследование расширенного неонатального скрининга 573 генов, связанных с тяжелыми наследственными заболеваниями, в Китае: результаты обследования 1127 новорожденных
2020-09-01
SCID: 54.1/dq7un6se
Discuss with AI
biochemical screeningcarrier frequenciesexpanded newborn screeninginherited metabolic diseasesnext-generation sequencing
Figures from the paper
Abstract (AI)
Background: Newborn screening (NBS) in China is mainly aimed at detecting biochemical levels of metabolites in the blood, which may generate false-positive/negative results. Current biochemical NBS includes tandem mass spectrometry (MS/MS) screening for metabolites as well as phenylalanine (Phe), thyroid-stimulating hormone (TSH), 17-α-hydroxyprogesterone (17-OHP), and glucose-6-phosphate dehydrogenase (G6PD) test. This study intended to explore whether next-generation sequencing (NGS) for dried blood spots combining with biochemical screening could improve the current screening efficiency and to investigate the carrier frequencies of mutations in causative genes related to amino acid metabolism, organic acid metabolism, and fatty acid oxidation in this cohort. Methods: We designed a panel of 573 genes related to severe inherited disorders and performed NGS in 1,127 individuals who had undergone biochemical NBS. The NGS screening results of neonates were used to compare with the biochemical results. Results: NGS screening results revealed that all the four newborns with abnormal G6PD values carried hemizygous G6PD mutations, which were consistent with the decreased G6PD enzymatic activity. The NGS results revealed an individual with compound heterozygous mutations of SLC22A5, who was biochemically negative in 2016. The MS/MS screening results in 2019 showed free carnitine deficiency, which was consistent with the genetic findings. The top five genes with the highest carrier frequencies of mutations in these newborns were PAH (1:56, 1.79%), ETFDH (1:81, 1.23%), MMACHC (1:87, 1.15%), SLC25A13 (1:102, 0.98%), and GCDH (1:125, 0.80%). Conclusions: Our study highlighted that combining NGS screening with biochemical screening could improve the current NBS efficiency. This is the first study to investigate carrier frequencies of mutations in 77 genes causing inherited metabolic diseases (IMDs) in China.
Key Findings
1
A 573-gene NGS panel was applied to dried blood spots from 1,127 Chinese newborns alongside conventional biochemical newborn screening.
2
All four newborns with abnormal G6PD measurements carried hemizygous G6PD mutations, confirming the biochemical findings.
3
NGS identified compound heterozygous SLC22A5 mutations in a newborn with initially negative biochemical screening; later MS/MS detected free carnitine deficiency.
4
The findings support combining NGS with biochemical screening to improve newborn-screening efficiency and provide carrier-frequency data for 77 IMD-related genes in China.
5
The five highest mutation carrier frequencies were observed for PAH (1:56), ETFDH (1:81), MMACHC (1:87), SLC25A13 (1:102), and GCDH (1:125).
Research Object
1,127 Chinese newborns undergoing expanded newborn screening for severe inherited disorders using a 573-gene NGS panel combined with biochemical screening
Research Subject
The screening efficiency, concordance with biochemical results, and carrier frequencies of pathogenic mutations associated with inherited metabolic diseases
Publication Details
Publication Date
2020-09-01
Journal
Publisher
ISSN
Open access PDF
Access Type
Author Information
Download PDF
Subscribe to digest