Analysis of clinical characteristics and SLC25A13 gene mutation in children with neonatal intrahepatic cholestasis caused by citrin deficiency / 国际儿科学杂志

Objective:To analyze the clinical characteristics and SLC25A13 gene mutation in children with neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD).Methods:The data of 18 children diagnosed with NICCD in Xi′an Children′s Hospital from January 2014 to December 2018 were collected.The clinical manifestations, biochemical characteristics, SLC25A13 gene mutation and prognosis were analyzed.Results:All the 18 cases of NICCD were from North China and the age of initial diagnosis averaged(63.4±19.5)days.The clinical manifestations included jaundice(100%), light yellow or white stool(38.9%), growth retardation(27.8%)and so on.All patients had cholestasis.Of 18 cases, the levels of glutamyltranspeptidase, total bile acid and alpha fetoprotein were all increased, and serum albumin was decreased.Elevated aspartate aminotransferase(94.4%), elevated glutamic pyruvic transaminase(72.2%), prolonged prothrombin time(88.9%), hyperlactemia(83.3%), hypoglycemia(77.8%), anemia(66.7%)and other biochemical abnormalities were observed.Citrulline and other serum amino acids of all cases were elevated in blood samples by tandem mass spectrometry.The increase of 4-hydroxyphenyllactate and 4-hydroxyphenylpyruvate was found in 70%(7/10)urine samples by gas chromatography.Age was negatively correlated with total bile acid( r=-0.469, P=0.049), and positively correlated with blood ammonia, threonine, methionine, ornithine and tyrosine( r=0.472, 0.690, 0.698, 0.678 and 0.769, respectively, P<0.05). A total of 16 SLC25A13 gene mutations were detected, of them c. 851_854del(33.3%)and c. 1638_1660dup(19.4%)were the most common.c.1841+ 3_1841+ 4del, c.980_981del(p.E327Vfs*45)and c. 602A>T(p.E201V)were novel mutations.Among the 17 children who were followed up, 1 case died and 16 cases had normal biochemical parameters within 1 year. Conclusion:The characteristic biochemical changes are helpful for early recognition of NICCD.The prognosis of NICCD is good if the treatment is appropriate and timely.c.851_854del and c. 1638_1660dup are high-frequency mutations of SLC25A13 gene in north China.

Analysis of a novel JAG1 variant and clinical phenotype in a family affected with Alagille syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a pedigree affected with Alagille syndrome (ALGS).@*METHODS@#Targeted capture and next generation sequencing was carried out for the proband. Candidate variants were verified by Sanger sequencing among his family members. Their pathogenicity of the variant was predicted with bioinformatic analysis. Clinical characteristics and genotype-phenotype correlation were analyzed.@*RESULTS@#The proband, his elder sister and mother were found to carry a heterozygous c.1270dupG (p.Ala424Glyfs*5) variant of the JAG1 gene, which may lead to premature termination of translation and a truncated protein with loss of function. The variant was unreported previously. The phenotypes of the proband (cholestasis, pulmonary artery stenosis and peculiar faces) have differed from those of his elder sister (cholestasis with pruritus, posterior embryonic ring of cornea) and mother (with no clinical manifestation). Cholestasis and peculiar face of the proband became insignificant with age.@*CONCLUSION@#The c.1270dupG (p.Ala424Glyfs*5) variant of the JAG1 gene probably underlay the ALGS in this pedigree with incomplete penetrance.

Recognizing the vaccination strategy of pertussis according to the family aggregation feature of transmission / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the age distribution of pertussis patients admitted in the children hospital and to analyze the source of infection as well as its transmission patterns.</p><p><b>METHODS</b>Patients visiting to the Children Hospital and epidemiologically related cases during Feb. 2012 to Aug. 2013 were tested to confirm the diagnosis. Excel 2007 software was used to analyze the age distribution and clinical symptoms of clinic cases, the source of infection or subsequent cases.</p><p><b>RESULTS</b>165 out of 254 clinically suspicious pertussis cases and 38 out of the 54 epidemiologically related cases were confirmed of having pertussis infection. There were 138 (83.6%) cases under 1 year of age in the confirmed clinical cases and 36 (94.7%) cases older than 20 years of age among the confirmed epidemiologically related pertussis cases. All the confirmed epidemiologically related cases were misdiagnosed or missed for diagnosis. As the source of pertussis infection in confirmed clinical cases, parents played an imported role among 25 of the 32 cases. Transmission from infants and/or little children to adults were also observed in this study.</p><p><b>CONCLUSION</b>Infants accounted for the most among the pertussis patients that visiting the clinics. Adults, being misdiagnosed or missed diagnosed, were the main sources of infection to infants. Epidemics of pertussis occurred under family aggregation. Further study was in need to develop the proper strategy for pertussis booster vaccination.</p>