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Objective To investigate the incidence of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in neonates with idiopathic neonatal cholestasis (INC) in Nanjing, China, SLC25A13 gene mutations in these neonates, and clinical features. Methods A total of 152 neonates with INC, who were admitted to the Affiliated Nanjing Children's Hospital of Nanjing Medical University from September 2009 to August 2013, underwent gene analysis for detecting SLC25A13 gene mutations. The neonates were divided into NICCD group, who had been diagnosed definitely, and INC group at a ratio of 1 : 2, considering the age and gender. Several biochemical indices were compared between the two groups. Comparison of continuous data between the two groups was made by Mann - Whitney U test after Bonferroni correction. Results There were 21 confirmed cases of NICCD (21/152, 13.82%) among the 152 neonates with INC; five types of SLC25A13 mutations were identified in the 21 neonates with NICCD, including 851_854del (27/42, 64. 29% ), IVS6 +5G → A (7/42, 16. 67% ), 1638ins23 (5/42, 11.90%), IVS11 +1G → A (2/42, 4.76%), and Q259X (1/42, 2.38%). The alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, bile acid concentration, albumin level, fasting blood glucose, blood ammonia, and prothrombin time for the NICCD group were 39.42 ±23.40 U/L, 124.85 ± 92.65U/L, 142.43 ± 24.34 μmol/L, 30.66 ±2.70 g/L, 2.79 ± 0.54 mmol/L, 117. 57±27.88 μmol/L, and 14.03 ±2.79 s, respectively, versus 136.02 ± 113.67 U/L, 226. 12 ±129.26 U/L, 80.47 ± 31,53 μmol/L, 36.87 ±4.96 g/L, 3. 14 ±0.45 mmol/L, 76.43 ±20.80 jmol/L, and 11.40 ± 1.55s for the INC group. The NICCD group had significantly lower ALT and AST levels than the INC group (Z = 5.02, P = 0.000; Z = 3. 66, P = 0. 000) ; the NICCD group had a significantly higher bile acid concentration than the INC group (Z = 5. 58, P=0.000); the NICCD group had significantly lower albumin level and fasting blood glucose than the INC group (Z=4.52, P = 0.000; Z = 2.56, P = 0.010) ; the NICCD group had a significantly higher blood ammonia level than the INC group (Z=4. 75, P = 0.000) ; the NICCD group had a significantly longer prothrombin time than the INC group (Z =4.10, P = 0.000). Conclusion Citrin deficiency due to SLC25A13 gene mutations is an important cause of INC in Nanjing. The three most common mutations are 851_854del, IVS6 +5 G > A, and 1638_1660dup23, which account for 92. 86% of the SLC25A13 gene mutations. More attention should be paid to clinical analysis and detection of SLC25A13 gene mutations to confirm the diagnosis of NICCD. [ABSTRACT FROM AUTHOR]

Variations in the JAGGED1 gene have been found to cause Alagille syndrome. Nevertheless, no particular hotspots in the gene have been found; any part of the entire coding regions for JAGGED1 may be involved. Twin sisters with jaundice visited our hospital and were diagnosed with Alagille syndrome. The gene variations in their JAGGED1 coding sequences were evaluated by complementary DNA sequencing. The 12-month-old twin sisters have broad foreheads, deep-set eyes, pointed chins, and triangular faces with jaundice. Clinical testing showed the presence of posterior embryotoxon, butterfly vertebrae, and atrial septal defect. Biochemical indexes showed cholestasis and liver damage. Three conserved variations were identified within exons 22 (c.2612C>G), 24 (c.2957T>A), and 26 (c.3417T>C) in the JAGGED1 coding sequence. The predicted consequences for c.2612C>G, c.2957T>A, and c.3417T>C were p.Pro871Arg, p.Leu986*, and p.Tyr1139=, respectively. The T to A change in the JAGGED1 coding sequence at 2957 will generate a stop codon and might lead to deletion of amino acid 233 at the C terminal of the JAGGED1 protein. Our data suggest that gene variations of c.2612C>G, c.2957T>A, and c.3417T>C, especially c.2957T>A, might have contributed to the pathogenesis of Alagille syndrome in these Chinese twin sisters and provided new gene evidences for Alagille syndrome.