Combining newborn metabolic and genetic screening for neonatal intrahepatic cholestasis caused by citrin deficiency
Yiming Lin
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Neonatal Disease Screening Center, Quanzhou Maternity and Children's Hospital, Quanzhou, China
Search for more papers by this authorYaru Liu
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Zhejiang University School of Medicine, Hangzhou, China
Search for more papers by this authorLin Zhu
Department of Translational Medicine, Hangzhou Genuine Clinical Laboratory Co. Ltd, Hangzhou, China
Search for more papers by this authorKaixing Le
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Zhejiang University School of Medicine, Hangzhou, China
Search for more papers by this authorYuyan Shen
Neonatal Disease Screening Center, Huaihua Maternal and Child Health Hospital, Huaihua, China
Search for more papers by this authorChiju Yang
Neonatal Disease Screening Center, Jining Maternal and Child Health Family Service Center, Jining, China
Search for more papers by this authorXigui Chen
Neonatal Disease Screening Center, Jining Maternal and Child Health Family Service Center, Jining, China
Search for more papers by this authorHaili Hu
Neonatal Disease Screening Center, Hefei Women and Children's Health Care Hospital, Hefei, China
Search for more papers by this authorQingqing Ma
Neonatal Disease Screening Center, Hefei Women and Children's Health Care Hospital, Hefei, China
Search for more papers by this authorXueqin Shi
Department of Pediatrics, Yancheng Maternity and Child Health Care Hospital, Yancheng, China
Search for more papers by this authorZhenzhen Hu
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Search for more papers by this authorJianbin Yang
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Search for more papers by this authorYaping Shen
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Search for more papers by this authorChien-Hsing Lin
Department of Research and Development, Feng Chi Biotech Corp, Taipei, Taiwan
Search for more papers by this authorChenggang Huang
Research and Development Center, Zhejiang Biosan Biochemical Technologies Co., Ltd, Hangzhou, China
Search for more papers by this authorCorresponding Author
Xinwen Huang
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Correspondence
Xinwen Huang, Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China.
Email: [email protected]
Search for more papers by this authorYiming Lin
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Neonatal Disease Screening Center, Quanzhou Maternity and Children's Hospital, Quanzhou, China
Search for more papers by this authorYaru Liu
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Zhejiang University School of Medicine, Hangzhou, China
Search for more papers by this authorLin Zhu
Department of Translational Medicine, Hangzhou Genuine Clinical Laboratory Co. Ltd, Hangzhou, China
Search for more papers by this authorKaixing Le
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Zhejiang University School of Medicine, Hangzhou, China
Search for more papers by this authorYuyan Shen
Neonatal Disease Screening Center, Huaihua Maternal and Child Health Hospital, Huaihua, China
Search for more papers by this authorChiju Yang
Neonatal Disease Screening Center, Jining Maternal and Child Health Family Service Center, Jining, China
Search for more papers by this authorXigui Chen
Neonatal Disease Screening Center, Jining Maternal and Child Health Family Service Center, Jining, China
Search for more papers by this authorHaili Hu
Neonatal Disease Screening Center, Hefei Women and Children's Health Care Hospital, Hefei, China
Search for more papers by this authorQingqing Ma
Neonatal Disease Screening Center, Hefei Women and Children's Health Care Hospital, Hefei, China
Search for more papers by this authorXueqin Shi
Department of Pediatrics, Yancheng Maternity and Child Health Care Hospital, Yancheng, China
Search for more papers by this authorZhenzhen Hu
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Search for more papers by this authorJianbin Yang
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Search for more papers by this authorYaping Shen
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Search for more papers by this authorChien-Hsing Lin
Department of Research and Development, Feng Chi Biotech Corp, Taipei, Taiwan
Search for more papers by this authorChenggang Huang
Research and Development Center, Zhejiang Biosan Biochemical Technologies Co., Ltd, Hangzhou, China
Search for more papers by this authorCorresponding Author
Xinwen Huang
Department of Genetics and Metabolism, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Correspondence
Xinwen Huang, Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou 310052, China.
Email: [email protected]
Search for more papers by this authorFunding information: the National Key Research and Development Program of China, Grant/Award Number: 2018YFC1002200
Abstract
To evaluate the feasibility of incorporating genetic screening for neonatal intrahepatic cholestasis, caused by citrin deficiency (NICCD), into the current newborn screening (NBS) program. We designed a high-throughput iPLEX genotyping assay to detect 28 SLC25A13 mutations in the Chinese population. From March 2018 to June 2018, 237 630 newborns were screened by tandem mass spectrometry at six hospitals. Newborns with citrulline levels between 1/2cutoff and cutoff values of the upper limit were recruited for genetic screening using the newly developed assay. The sensitivity and specificity of the iPLEX genotyping assay both reached 100% in clinical practice. Overall, 29 364 (12.4%) newborns received further genetic screening. Five patients with conclusive genotypes were successfully identified. The most common SLC25A13 mutation was c.851_854del, with an allele frequency of 60%. In total, 658 individuals with one mutant allele were identified as carriers. Eighteen different mutations were observed, yielding a carrier rate of 1/45. Notably, Quanzhou in southern China had a carrier rate of up to 1/28, whereas Jining in northern China had a carrier rate higher than that of other southern and border cities. The high throughput iPLEX genotyping assay is an effective and reliable approach for NICCD genotyping. The combined genetic screening could identify an additional subgroup of patients with NICCD, undetectable by conventional NBS. Therefore, this study demonstrates the viability of incorporating genetic screening for NICCD into the current NBS program.
CONFLICT OF INTEREST
L.Z. is currently an employee of Hangzhou Genuine Clinical Laboratory Co. Ltd. C.H.L. is currently an employee of Feng Chi Biotech Corp. C.G.H. is currently an employee of Zhejiang Biosan Biochemical Technologies Corp. The other authors declare that they have no conflicts of interest.
Supporting Information
| Filename | Description |
|---|---|
| JIMD_12206_Supplementary file 1.docxWord 2007 document , 18.8 KB | Table S1 Customized panels based on reported SLC25A13 mutations |
| JIMD_12206_Supplementary file 2-The estimation of target sample size.pdfPDF document, 363.9 KB | Data S1 Supporting information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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