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. 2022 Feb 21;17(1):66.
doi: 10.1186/s13023-022-02231-x.

Application of a next-generation sequencing (NGS) panel in newborn screening efficiently identifies inborn disorders of neonates

Xinwen Huang #  1 , Dingwen Wu #  1   2 , Lin Zhu  3 , Wenjun Wang  3 , Rulai Yang  1 , Jianbin Yang  1 , Qunyan He  4 , Bingquan Zhu  1   5 , Ying You  4 , Rui Xiao  6 , Zhengyan Zhao  7   8
Affiliations

Application of a next-generation sequencing (NGS) panel in newborn screening efficiently identifies inborn disorders of neonates

Xinwen Huang et al. Orphanet J Rare Dis. .

Abstract

Background: Newborn screening (NBS) has been implemented for neonatal inborn disorders using various technology platforms, but false-positive and false-negative results are still common. In addition, target diseases of NBS are limited by suitable biomarkers. Here we sought to assess the feasibility of further improving the screening using next-generation sequencing technology.

Methods: We designed a newborn genetic sequencing (NBGS) panel based on multiplex PCR and next generation sequencing to analyze 134 genes of 74 inborn disorders, that were validated in 287 samples with previously known mutations. A retrospective cohort of 4986 newborns was analyzed and compared with the biochemical results to evaluate the performance of this panel.

Results: The accuracy of the panel was 99.65% with all samples, and 154 mutations from 287 samples were 100% detected. In 4986 newborns, a total of 113 newborns were detected with biallelic or hemizygous mutations, of which 36 newborns were positive for the same disorder by both NBGS and conventional NBS (C-NBS) and 77 individuals were NBGS positive/C-NBS negative. Importantly, 4 of the 77 newborns were diagnosed currently including 1 newborn with methylmalonic acidemia, 1 newborn with primary systemic carnitine deficiency and 2 newborns with Wilson's disease. A total of 1326 newborns were found to be carriers with an overall carrier rate of 26.6%.

Conclusion: Analysis based on next generation sequencing could effectively identify neonates affected with more congenital disorders. Combined with C-NBS, this approach may improve the early and accurate identification of neonates with inborn disorders. Our study lays the foundation for prospective studies and for implementing NGS-based analysis in NBS.

Keywords: Gene mutation; Inherited disorders; Multiple PCR; Newborn genetic screening.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Newborn genetic screening of the retrospective cohort.) Comparison of C-NBS and NBGS result in 4981 recruited newborns; b The work flow of NBGS panel
Fig. 2
Fig. 2
Diagnosed and C-NBS negative newborns identified by NBGS. a Genetic analysis of the 53 diagnosed newborns by NBGS; b The distribution of 77 C-NBS negative newborns that detected positive by NBGS panel (the red boxes represent diagnosed newborns)
Fig. 3
Fig. 3
The mutation frequency in carriers and biochemical index of ASS1 and MCCC1 carriers. a The numbers of variants in carriers. b The distribution of high frequency gene mutations in carriers. c Cit concentration in ASS1 gene mutation carriers and negative control. d C4DC + C5OH concentration in MCCC1 gene mutation carriers and negative control
See this image and copyright information in PMC

References

    1. Rajabi F. Updates in newborn screening. Pediatr Ann. 2018;47(5):e187–e190. - PubMed
    1. Patel H, Feldman M. Universal newborn hearing screening. Paediatr Child Health. 2011;16(5):301–310. - PMC - PubMed
    1. Watson MS, Mann MY, Lloyd-Puryear MA, Rinaldo P, Howell RR, American College of Medical Genetics Newborn Screening Expert Group Newborn screening: toward a uniform screening panel and system–executive summary. Pediatrics. 2006;117(5 Pt 2):S296–307. - PubMed
    1. Urv TK, Parisi MA. Newborn screening: beyond the spot. Adv Exp Med Biol. 2017;1031:323–346. - PubMed
    1. Honzík T, et al. Carnitine concentrations in term and preterm newborns at birth and during the first days of life. Prague Med Rep. 2005;106(3):297–306. - PubMed

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