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The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

SLC25A13 gene mutations cause citrin deficiency, which leads to neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). Information on the mutation spectrum of SLC25A13 in the Chinese population is limited. The aim of this study was to explore the mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and various forms of aminoacidemia.

Methods

Sequence analyses were performed on 39 infants with intrahepatic cholestasis and various forms of aminoacidemia. Novel mutations were subjected to homology and structural analyses. Western blots were performed when liver specimens available.

Results

Genetic testing revealed the presence of SLC25A13 gene mutations (9 heterozygotes, 6 homozygotes and 13 compound heterozygotes) in 28 infants. Subsequent Western blot analysis revealed 22 cases of citrin deficiency, accounting for 56.4% of the 39 patients. Twelve types of mutations, including nine known mutations and three novel mutations, were found. Of the 49 mutated alleles, known ones include 851del4 (26 alleles, 53.1%), 1638ins23 (6 alleles, 12.2%), IVSl6ins3kb (3 alleles, 6.1%), IVS6+5G>A (2 alleles, 4.1%), E601K (2 alleles, 4.1%) and IVS11+1G>A, R184X, R360X and R585H (1 allele each, 2.0%). The three novel mutations were a splice site change (IVS6+1G>A), a deletion mutation (1092_1095delT) and a missense mutation (L85P), each in one allele.

Conclusions

The mutation spectrum of the SLC25A13 gene in a Chinese population of infants with intrahepatic cholestasis with various forms of aminoacidemia was found to be different from that of other population groups in East Asia. The SLC25A13 gene mutation is the most important cause of infantile intrahepatic cholestasis with various forms of aminoacidemia.

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Acknowledgments

We thank MSc Ms. LJ Fang and R Chen for carrying out the mutation test for IVSl6ins3kb, and Prof. YK Leung for the revision and editing of the manuscript. We also thank the patients and their parents for their kind cooperation as well as the physicians who referred the patients. This paper was partly supported by two grants (Nos. 30672257 and 30973230) from the National Natural Science Foundation of China and a grant for Shanghai Public Health Key Subject Construction (08GWZX0102), and was supported in part by a Grant for Asia-Africa Scientific Platform Program from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. The Center for Pediatric Liver Diseases, Children’s Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai, 201102, People’s Republic of China

    Hai-Yan Fu, Shao-Ren Zhang, Xiao-Hong Wang & Jian-She Wang

  2. The Department of Pediatrics, Shanghai Medical College of Fudan University, Shanghai, 201102, People’s Republic of China

    Hai-Yan Fu, Shao-Ren Zhang, Xiao-Hong Wang & Jian-She Wang

  3. Institute for Health Sciences, Tokushima Bunri University, Tokushima, 770-8514, Japan

    Takeyori Saheki

  4. Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan

    Keiko Kobayashi

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  1. Hai-Yan Fu
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Correspondence to Jian-She Wang.

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Fu, HY., Zhang, SR., Wang, XH. et al. The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia. J Gastroenterol 46, 510–518 (2011). https://doi.org/10.1007/s00535-010-0329-y

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