Journal
ONCOTARGET
Volume 8, Issue 50, Pages 87182-87193Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19901
Keywords
citrin deficiency; intrahepatic cholestasis; SLC25A13; mutation; Western blotting
Categories
Funding
- Fund for the construction of high-level Universities in Guangdong province [11615470]
- Fundamental Research Funds for the Central Universities [21615470]
- Natural Science foundation of Guangdong Province [2016A030313099]
- National Natural Science Foundation (NSFC) of China [81270957, 81570793, 81670813]
Ask authors/readers for more resources
Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) arises from biallelic SLC25A13 mutations, and SLC25A13 analysis provides reliable evidences for NICCD definite diagnosis. However, novel large insertions/deletions in this gene could not be detected just by conventional DNA analysis. This study aimed to explore definite diagnostic evidences for an infant highly-suspected to have NICCD. Prevalent mutation screening and Sanger sequencing of SLC25A13 gene just revealed a paternally-inherited mutation c. 851_854del4. Nevertheless, neither citrin protein nor SLC25A13 transcripts of maternal origin could be detected on Western blotting and cDNA cloning analysis, respectively. On this basis, the hidden maternal mutation was precisely positioned using SNP analysis and semi-quantitative PCR, and finally identified as a novel large deletion c.-3251_c.15+18443del21709bp, which involved the SLC25A13 promoter region and the entire exon 1 where locates the translation initiation codon. Hence, NICCD was definitely diagnosed in the infant. To the best of our knowledge, the novel gross deletion, which silenced the transcriptional and translational expression of the affected SLC25A13 allele, is the hitherto largest deletion in SLC25A13 mutation spectrum. The Western blotting approach using mitochondrial protein extracted from expanded peripheral blood lymphocytes, of particular note, might be a new minimally-invasive and more-feasible molecular tool for NICCD diagnosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available