Chen S.-T.Su Y.-N.YEN-HSUAN NIWUH-LIANG HWUNI-CHUNG LEEYIN-HSIU CHIENChang C.-C.HUEY-LING CHENMEI-HWEI CHANG2021-01-042021-01-0420120022-3476https://www.scopus.com/inward/record.uri?eid=2-s2.0-84866729980&doi=10.1016%2fj.jpeds.2012.03.038&partnerID=40&md5=5e79a25d80cdde73d98392cd5bc48e51https://scholars.lib.ntu.edu.tw/handle/123456789/536989Objective: To assess the diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) by using high-resolution melting (HRM) analysis and a clinical scoring system. Study design: Genetic variations in the 18 coding exons were prescreened using HRM analysis and then confirmed by direct sequencing. To establish a scoring system, clinical features of 20 patients with NICCD diagnosed in Taiwan between the years 2000 and 2008 were compared with those of 47 patients with biliary atresia and 35 with infantile cholestasis. Results: Eight types of mutations/polymorphisms were identified in patients with NICCD, including 5 mutations in the coding region or splice site (c.851del4, c.1638ins23, R553Q, IVS6+5G > A, IVS11+1G > A), and 3 single-nucleotide polymorphisms (IVS11+17C > G, IVS4+6A > G/rs6957975, and c.1194A > G/rs2301629). The 3 hotspot mutations (c.851del4, c.1638ins23, and IVS6+5G > A) comprised 33/35 (94.3%) mutated alleles. The patients with NICCD had a higher frequency of the rs6957975 polymorphism compared with 103 healthy controls (P <.0001). A 6-point scoring system was proposed according to clinical parameters. The patients with NICCD tended to score ?4 points, whereas biliary atresia and other infantile cholestasis tended to score <4 points (P <.0001). Conclusions: HRM analysis was efficient and effective in detecting mutations. Three common mutations comprised the majority of mutations found in our patients. The IVS4+6A > G polymorphism was associated with NICCD. A scoring system may help to differentiate patients with NICCD from those with biliary atresia. Copyright ? 2012 Mosby Inc.[SDGs]SDG3alanine aminotransferase; aspartate aminotransferase; bilirubin; carrier protein; eriodictyol 7 o glucoside; gamma glutamyltransferase; unclassified drug; allele; article; aspartate aminotransferase blood level; bile duct atresia; bilirubin blood level; clinical article; clinical feature; controlled study; diagnostic accuracy; diarrhea; exon; female; gamma glutamyl transferase blood level; gene frequency; gene mutation; genetic variability; heterozygosity; high resolution melting analysis; homozygosity; human; intrahepatic cholestasis; jaundice; male; neonatal intrahepatic cholestasis caused by citrin deficiency; newborn; newborn disease; nucleotide sequence; predictive value; priority journal; protein deficiency; prothrombin time; single nucleotide polymorphism; Taiwanjournal article10.1016/j.jpeds.2012.03.038225752532-s2.0-84866729980