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Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg)

  • Authors:
    • Hua Li
    • Mei Deng
    • Li Guo
    • Jian‑Wu Qiu
    • Gui‑Zhi Lin
    • Xiao‑Ling Long
    • Xiao‑Min Xiao
    • Yuan‑Zong Song
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Pediatrics, Bo‑Ai Hospital of Zhongshan, Zhongshan, Guangdong 528400, P.R. China, Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4915-4924
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    Published online on: October 23, 2019
       https://doi.org/10.3892/mmr.2019.10763
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Abstract

Sodium taurocholate cotransporting polypeptide (NTCP), a carrier protein encoded by solute carrier family 10 member 1 (SLC10A1), is expressed in the basolateral membrane of hepatocytes, where it is responsible for the uptake of bile acids from plasma into hepatocytes. The first patient with NTCP deficiency was described in 2015. A limited number of such patients have been reported in the literature and their genotypic and phenotypic features require further investigation. The current study investigated 4 patients with NTCP deficiency from two unrelated families. The patients were subjected to SLC10A1 genetic analysis and it was revealed that all patients were compound heterozygous for the c.800C>T (p.Ser267Phe) and c.595A>C (p.Ser199Arg) SLC10A1 variants. To the best of the authors' knowledge, the latter variant had not been previously reported. Further analysis in 50 healthy individuals did not identify carriers. The c.595A>C (p.Ser199Arg) variant exhibited co‑segregation with hypercholanemia and exhibited a relatively conserved amino acid when compared with homologous peptides. Moreover, SWISS‑MODEL prediction revealed that the mutation affected the conformation of the NTCP molecule. The 4 patients demonstrated varying degrees of hypercholanemia while a downward trend in the plasma levels of total bile acids (TBA) in 2 pediatric patients and occasionally normal TBA level in an adult case were observed. The results indicated an autosomal recessive trait for NTCP deficiency, supported the primary role of NTCP in the uptake of bile acids from plasma and suggested that hepatic uptake of bile acids may occur by means other than NTCP uptake. Moreover, the novel missense variant c.595A>C(p.Ser199Arg) enriched the SLC10A1 mutation spectrum and may serve as a new genetic marker for the molecular diagnosis and genetic counseling of NTCP deficiency.
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Copy and paste a formatted citation
Spandidos Publications style
Li H, Deng M, Guo L, Qiu JW, Lin GZ, Long XL, Xiao XM and Song YZ: Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg). Mol Med Rep 20: 4915-4924, 2019.
APA
Li, H., Deng, M., Guo, L., Qiu, J., Lin, G., Long, X. ... Song, Y. (2019). Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg). Molecular Medicine Reports, 20, 4915-4924. https://doi.org/10.3892/mmr.2019.10763
MLA
Li, H., Deng, M., Guo, L., Qiu, J., Lin, G., Long, X., Xiao, X., Song, Y."Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg)". Molecular Medicine Reports 20.6 (2019): 4915-4924.
Chicago
Li, H., Deng, M., Guo, L., Qiu, J., Lin, G., Long, X., Xiao, X., Song, Y."Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg)". Molecular Medicine Reports 20, no. 6 (2019): 4915-4924. https://doi.org/10.3892/mmr.2019.10763
Copy and paste a formatted citation
x
Spandidos Publications style
Li H, Deng M, Guo L, Qiu JW, Lin GZ, Long XL, Xiao XM and Song YZ: Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg). Mol Med Rep 20: 4915-4924, 2019.
APA
Li, H., Deng, M., Guo, L., Qiu, J., Lin, G., Long, X. ... Song, Y. (2019). Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg). Molecular Medicine Reports, 20, 4915-4924. https://doi.org/10.3892/mmr.2019.10763
MLA
Li, H., Deng, M., Guo, L., Qiu, J., Lin, G., Long, X., Xiao, X., Song, Y."Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg)". Molecular Medicine Reports 20.6 (2019): 4915-4924.
Chicago
Li, H., Deng, M., Guo, L., Qiu, J., Lin, G., Long, X., Xiao, X., Song, Y."Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg)". Molecular Medicine Reports 20, no. 6 (2019): 4915-4924. https://doi.org/10.3892/mmr.2019.10763
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