Analysis Of UGT1A1 Gene Variants In Eight Patients With Crigler-Najjar Syndrome Type Ⅱ

ObjectiveThe purpose of this study was to detect and identify UGT1A1 gene variation in patients with clinically diagnosed Crigler-Najjar syndrome Type Ⅱ,clarify the diagnosis of CNS-Ⅱ,preliminarily explore the relationship between genotype and phenotype,understand the characteristics of CNS-Ⅱ complicated with extrahepatic diseases,and improve the understanding of this disease.MethodsClinical data were collected from 8 unrelated probands and some family members of Crigler-Najjar syndrome type Ⅱ families,and UGT1A1 gene variation was detected by Sanger sequencing.OutcomesThe 8 probands clinically diagnosed as CNS-Ⅱ included 2 males and6 females,with an average age of 39.12±9.4 years.The most common clinical manifestations were yellow skin staining(8/8,100%),followed by abdominal distension(1/8,12.5%)and abdominal pain(1/8,12.5%).The average total bilirubin was 191.4±100.8μmol/L,and the average indirect bilirubin was 175.4±99.43μmol/L.UGT1A1 gene was detected in 8 proband cases,and 8 different mutations were detected,including C.-3279T>G,A(TA)7TAA,C.455C>T,C.211G>A,C.686C>A,C.1456T>G,C.1091C>T,C.1387G>A.Among them,c.455C>T and C.1387G>A were newly discovered possible pathogenicity variants.Conclusions1.The present study clarified the genetic diagnosis at the genomic level for 8 prevalent patients with a clinical diagnosis of CNS-Ⅱ.c.1456T>G(p.Y486D)was the most common pathogenic variant in this group of CNS-Ⅱ.Meanwhile,two previously unreported novel variants c.455C>T(p.P152L)and c.1387G>A(p.E463K)were identified,broadening the spectrum of variants in the UGT1A1 gene in the Chinese population.2.Variants that are common in Eastern populations and have an impact on UGT enzyme activity: c.211G>A(p.G71R)(TA)7TAA and c.-3279T>G,c.686C>A(p.P229Q)and the superposition of these variants can exacerbate the jaundice phenotype of patients.