Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep;8(17):1058.
doi: 10.21037/atm-20-1147.

A pilot study of expanded newborn screening for 573 genes related to severe inherited disorders in China: results from 1,127 newborns

Xiaomei Luo  1 , Yu Sun  1 , Feng Xu  1 , Jun Guo  1 , Lin Li  2 , Zhiwei Lin  2 , Jun Ye  1 , Xuefan Gu  1 , Yongguo Yu  1   3
Affiliations

A pilot study of expanded newborn screening for 573 genes related to severe inherited disorders in China: results from 1,127 newborns

Xiaomei Luo et al. Ann Transl Med. 2020 Sep.

Abstract

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.

Keywords: Expanded newborn screening (NBS); carrier frequencies; inherited disorders; inherited metabolic diseases (IMDs); next-generation sequencing (NGS).

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-1147). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Sequencing analysis of the SLC22A5 gene mutations. The arrows show the site of the c.760 and c.1400 of the family.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ombrone D, Giocaliere E, Forni G, et al. Expanded newborn screening by mass spectrometry: New tests, future perspectives. Mass Spectrom Rev 2016;35:71-84. 10.1002/mas.21463 - DOI - PubMed
    1. Holm IA, Agrawal PB, Ceyhan-Birsoy O, et al. The BabySeq project: implementing genomic sequencing in newborns. BMC Pediatr 2018;18:225. 10.1186/s12887-018-1200-1 - DOI - PMC - PubMed
    1. Berg JS, Agrawal PB, Bailey DB, Jr, et al. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics 2017;139:e20162252. 10.1542/peds.2016-2252 - DOI - PMC - PubMed
    1. Ceyhan-Birsoy O, Murry JB, Machini K, et al. Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. Am J Hum Genet 2019;104:76-93. 10.1016/j.ajhg.2018.11.016 - DOI - PMC - PubMed
    1. Meng L, Pammi M, Saronwala A, et al. Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management. JAMA Pediatr 2017;171:e173438. 10.1001/jamapediatrics.2017.3438 - DOI - PMC - PubMed