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© 2022. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Introduction

Citrullinemia Type 1 (CTLN1) is an autosomal recessive disorder caused by variants in the ASS1 gene. This study intends to clarify the etiology of false positives in newborn screening for citrullinemia.

Method

Newborns who had elevated dried-blood spot citrulline levels were enrolled, and medical records were reviewed retrospectively. Common ASS1 variants were screened using high-resolution melting analysis.

Result

Between 2011 and 2021, 130 newborns received confirmatory testing for citrullinemia, 4 were found to be patients for CTLN1; 11 were patients with citrin deficiency; and 49 newborns were confirmed to be carrying one pathogenic ASS1 variant. The incidence of CTLN1 was 1 in 188,380 (95% confidence interval: 1 in 73,258 to 1 in 484,416). All ASS1 variants studied in this cohort were located in exons 11 to 15, which encode the tetrameric interface regions of the ASS1 protein. Among 10 ASS1 carriers with elevated citrulline levels and complete sequence data, four (40%) revealed additional non-benign ASS1 variants; in contrast, only 2 of the 26 controls (7.7%), with normal citrulline levels, had additional ASS1 variants.

Conclusion

Heterozygote ASS1 variants may lead to a mild elevation of blood citrulline levels: about 2–6 times the population mean. Molecular testing and family studies remain critical for precise diagnosis, genetic counseling, and management.

Details

Title
Asymptomatic ASS1 carriers with high blood citrulline levels
Author
Hui-An, Chen 1   VIAFID ORCID Logo  ; Hsu, Rai-Hseng 2 ; Kai-Ling, Chang 3 ; Yi-Chen, Huang 3 ; Yun-Chen, Chiang 3 ; Ni-Chung, Lee 2   VIAFID ORCID Logo  ; Wuh-Liang Hwu 2 ; Pao-Chin Chiu 4 ; Yin-Hsiu Chien 2   VIAFID ORCID Logo 

 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 
 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan 
 Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan 
 Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 
Section
ORIGINAL ARTICLES
Publication year
2022
Publication date
Sep 2022
Publisher
John Wiley & Sons, Inc.
e-ISSN
23249269
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2715115479
Copyright
© 2022. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.