Brief Article
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World J Gastroenterol. Jul 28, 2013; 19(28): 4545-4551
Published online Jul 28, 2013. doi: 10.3748/wjg.v19.i28.4545
Different regional distribution of SLC25A13 mutations in Chinese patients with neonatal intrahepatic cholestasis
Rui Chen, Xiao-Hong Wang, Hai-Yan Fu, Shao-Ren Zhang, Kuerbanjiang Abudouxikuer, Takeyori Saheki, Jian-She Wang
Rui Chen, Xiao-Hong Wang, Hai-Yan Fu, Shao-Ren Zhang, Kuerbanjiang Abudouxikuer, Jian-She Wang, Center for Pediatric Liver Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
Takeyori Saheki, Institute for Health Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan
Jian-She Wang, Department of Pediatrics, Jinshan Hospital, Fudan University, Shanghai 201508, China
Author contributions: Chen R, Fu HY, Zhang SR and Abudouxikuer K collected the samples and performed the gene tests and Western blotting; Chen R wrote the first graft of this paper; Wang XH conducted the follow up study and supported the funding; Wang JS designed and supervised the research and supported the funding; all authors contributed to the data analysis, revising and approving the final paper to be published.
Supported by National Natural Science Foundation of China, No. 30973230 and No. 81070281
Correspondence to: Jian-She Wang, Professor of Medicine, Department of Pediatrics, Jinshan Hospital, Fudan University, No. 391 Jinyi Road, Jinshan District, Shanghai 201508, China. jshwang@shmu.edu.cn
Telephone: +86-21-64931171 Fax: +86-21-64931171
Received: March 3, 2013
Revised: April 24, 2013
Accepted: June 1, 2013
Published online: July 28, 2013
Processing time: 149 Days and 0.2 Hours
Abstract

AIM: To investigate the differences in the mutation spectra of the SLC25A13 gene mutations from specific regions of China.

METHODS: Genetic analyses of SLC25A13 mutations were performed in 535 patients with neonatal intrahepatic cholestasis from our center over eight years. Unrelated infants with at least one mutant allele were enrolled to calculate the proportion of SLC25A13 mutations in different regions of China. The boundary between northern and southern China was drawn at the historical border of the Yangtze River.

RESULTS: A total of 63 unrelated patients (about 11% of cases with intrahepatic cholestasis) from 16 provinces or municipalities in China had mutations in the SLC25A13 gene, of these 16 (25%) were homozygotes, 28 (44%) were compound heterozygotes and 19 (30%) were heterozygotes. In addition to four well described common mutations (c.851_854del, c.1638_1660dup23, c.615+5G>A and c.1750+72_1751-4dup17insNM_138459.3:2667 also known as IVS16ins3kb), 13 other mutation types were identified, including three novel mutations: c.985_986insT, c.287T>C and c.1349A>G. According to the geographical division criteria, 60 mutant alleles were identified in patients from the southern areas of China, 43 alleles were identified in patients from the border, and 4 alleles were identified in patients from the northern areas of China. The proportion of four common mutations was higher in south region (56/60, 93%) than that in the border region (34/43, 79%, χ2 = 4.621, P = 0.032) and the northern region (2/4, 50%, χ2 = 8.288, P = 0.041).

CONCLUSION: The SLC25A13 mutation spectra among the three regions of China were different, providing a basis for the improvement of diagnostic strategies and interpretation of genetic diagnosis.

Keywords: Citrin deficiency; Mutation spectrum; Intrahepatic cholestasis; SLC25A13

Core tip: Genetic testing of SLC25A13 gene was performed in individuals from southern, border and northern regions of China. The proportion of four common mutations was significant higher in southern region than in the border region and the northern region, so mutation screening for the common 4 mutations an appropriate test in the southern region. In the border and northern region, DNA sequencing is probably more practical.