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The mutation spectrum of SLC25A13 gene in citrin deficiency: identification of novel mutations in Vietnamese pediatric cohort with neonatal intrahepatic cholestasis

Journal of Human Genetics volume 68, pages 305–312 (2023)Cite this article

Subjects

Abstract

Background

Citrin deficiency (CD), a disorder caused by mutations in the SLC25A13 gene, may result in neonatal intrahepatic cholestasis. This study was purposely to explore the mutation spectrum of SLC25A13 gene in Vietnamese CD patients.

Methods

The 292 unrelated CD patients were first screened for four high-frequency mutations by PCR/PCR-RFLP. Then, Sanger sequencing was performed directly for heterozygous or undetected patients. Novel mutations identified would need to be confirmed by their parents.

Results

12 pathogenic SLC25A13 mutations were identified in all probands, including three deletions c.851_854del (p.R284Rfs*3), c.70-63_133del (p.Y24_72Ifs*10), and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]), two splice-site mutations (IVS6+5G>A and IVS11+1G>A), one nonsense mutations c.1399C>T (p.R467*), one duplication mutation c.1638_1660dup (p.A554fs*570), one insertion IVSl6ins3kb (p.A584fs*585), and four missense mutation c.2T>C (p.M1T), c.1231G>A (p.V411M), c.1763G>A (p.R588Q), and c.135G>C (p.L45F). Among them, c.851_854del (mut I) was the most identified mutant allele (91.78%) with a total of 247 homozygous and 42 heterozygous genotypes of carriers. Interestingly, two novel mutations were identified: c.70-63_133del (p.Y24_72Ifs*10) and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]).

Conclusion

The SLC25A13 mutation spectrum related to intrahepatic cholestasis infants in Vietnam revealed a quite similar pattern to Asian countries’ reports. This finding supports the use of targeted SLC25A13 mutation for CD screening in Vietnam and contributed to the SLC25A13 mutation spectra worldwide. It also helps emphasize the role of DNA analysis in treatment, genetic counseling, and prenatal diagnosis.

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Data availability

The datasets generated and analyzed during the current study are available in the ClinVar repository, accession numbers to datasets: SCV002546525-SCV002546535 and SCV002546358.

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Acknowledgements

The authors appreciate the participation of the patient’s family in this study. This work was supported by the Vietnam National Children’s Hospital, Ministry of Health.

Author information

Authors and Affiliations

  1. Human Genetics Department, National Children’s Hospital, Hanoi, Vietnam

    Mai-Huong Thi Nguyen, Diem-Ngoc Ngo, Phuong-Mai Thi Nguyen & Minh-Dien Tran

  2. Hepatology Department, National Children’s Hospital, Hanoi, Vietnam

    Anh-Hoa Pham Nguyen & Minh-Dien Tran

  3. Gene Solutions, Ho Chi Minh City, Vietnam

    Hung-Sang Tang & Hoa Giang

  4. Medical Genetics Institutes, Ho Chi Minh City, Vietnam

    Hung-Sang Tang, Hoa Giang, Y-Thanh Lu & Hoai-Nghia Nguyen

  5. University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam

    Hoai-Nghia Nguyen

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Contributions

M-HNT designed the study, coordinated the study, analyzed data, and wrote the manuscript. A-HNP examined the patients and collected the samples. P-MNT and D-NN performed experiments. H-ST, HG, H-NN, and Y-TL helped with manuscript preparation. M-DT helped to revise the manuscript. All authors reviewed the manuscript.

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Correspondence to Mai-Huong Thi Nguyen.

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The authors declare no competing interests.

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All the methods were obtained in accordance with relevant guidelines and regulations and approved by the Research Institute for Child Health (RICH) - Vietnam National Children’s Hospital (VNCH) and Hanoi University of Public Health (HUPH), Ministry of Health, Hanoi, Vietnam. Informed consent for genetic analysis was obtained from the child’s parent or guardian prior.

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Nguyen, MH.T., Nguyen, AH.P., Ngo, DN. et al. The mutation spectrum of SLC25A13 gene in citrin deficiency: identification of novel mutations in Vietnamese pediatric cohort with neonatal intrahepatic cholestasis. J Hum Genet 68, 305–312 (2023). https://doi.org/10.1038/s10038-022-01112-2

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