Crigler-Najjar syndrome(CNS)and Gilbert syndrome(GS;OMIM:143500)are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity.Crigler-Najjar syndrome type 2(C...Crigler-Najjar syndrome(CNS)and Gilbert syndrome(GS;OMIM:143500)are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity.Crigler-Najjar syndrome type 2(CNS2;OMIM:606785)increases the risk of gallbladder stone formation and cholecystitis,while GS seldom causes health issues.We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth.CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)7TAA(rs3064744)and P229Q(rs35350960)in the UGT1A1 gene.After pedigree investigation,we found that the patient’s parents with modestly increased bilirubin had compound heterozygous mutations A(TA)7TAA and P229Q,which were GS.Bioinformatics analysis showed that A(TA)7TAA is in the TATA-box region of the gene UGT1A1 promoter,affecting gene transcriptional initiation,whereas P229Q modifies protein three-dimensional structure and may be harmful.In this pedigree,double homozygous mutations have a more severe phenotype than compound heterozygous mutations.Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction,and early bilirubin reduction(<103µmol/L(6 mg/dL))may reduce the risk of complications like cholecystitis in CNS2 patients,though further studies with longer follow-up are needed to confirm this observation.展开更多
The mutation is a critical element in determining the proteins’stability,becoming a core element in portraying the effects of a drug in the pharmaceutical industry.Doing wet laboratory tests to provide a better persp...The mutation is a critical element in determining the proteins’stability,becoming a core element in portraying the effects of a drug in the pharmaceutical industry.Doing wet laboratory tests to provide a better perspective on protein mutations is expensive and time-intensive since there are so many potential muta-tions,computational approaches that can reliably anticipate the consequences of amino acid mutations are critical.This work presents a robust methodology to analyze and identify the effects of mutation on a single protein structure.Initially,the context in a collection of words is determined using a knowledge graph for feature selection purposes.The proposed prediction is based on an easier and sim-pler logistic regression inferred binary classification technique.This approach can able to obtain a classification accuracy(AUC)Area Under the Curve of 87%when randomly validated against experimental energy changes.Moreover,for each cross-fold validation,the precision,recall,and F-Score are presented.These results support the validity of our strategy since it performs the vast majority of prior studies in this domain.展开更多
基金supported by the Fujian Province Natural Science Fund Project(Nos.2024J011017,2023J011846,2023J011159,2024Y0033,and 2024J08263)Joint Funds for the Innovation of Science and Technology in Fujian Province(Nos.2023Y9284 and 2023Y9305)+3 种基金the Fujian Provincial Health Commission Science and Technology Program(Nos.2024GGA090 and 2024QNA002)the Fujian Province Medical Innovation Foundation(No.2022CXA001)Startup Fund for Scientific Research,Fujian Medical University(Nos.2022QH2042 and 2023QH2038)National Famous and Old Chinese Medicine Experts(Xuemei Zhang,Xiaohua Yan,Shaoguang Lv,and Chunjin Yi)Inheritance Studio Construction Project.
文摘Crigler-Najjar syndrome(CNS)and Gilbert syndrome(GS;OMIM:143500)are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity.Crigler-Najjar syndrome type 2(CNS2;OMIM:606785)increases the risk of gallbladder stone formation and cholecystitis,while GS seldom causes health issues.We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth.CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)7TAA(rs3064744)and P229Q(rs35350960)in the UGT1A1 gene.After pedigree investigation,we found that the patient’s parents with modestly increased bilirubin had compound heterozygous mutations A(TA)7TAA and P229Q,which were GS.Bioinformatics analysis showed that A(TA)7TAA is in the TATA-box region of the gene UGT1A1 promoter,affecting gene transcriptional initiation,whereas P229Q modifies protein three-dimensional structure and may be harmful.In this pedigree,double homozygous mutations have a more severe phenotype than compound heterozygous mutations.Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction,and early bilirubin reduction(<103µmol/L(6 mg/dL))may reduce the risk of complications like cholecystitis in CNS2 patients,though further studies with longer follow-up are needed to confirm this observation.
文摘The mutation is a critical element in determining the proteins’stability,becoming a core element in portraying the effects of a drug in the pharmaceutical industry.Doing wet laboratory tests to provide a better perspective on protein mutations is expensive and time-intensive since there are so many potential muta-tions,computational approaches that can reliably anticipate the consequences of amino acid mutations are critical.This work presents a robust methodology to analyze and identify the effects of mutation on a single protein structure.Initially,the context in a collection of words is determined using a knowledge graph for feature selection purposes.The proposed prediction is based on an easier and sim-pler logistic regression inferred binary classification technique.This approach can able to obtain a classification accuracy(AUC)Area Under the Curve of 87%when randomly validated against experimental energy changes.Moreover,for each cross-fold validation,the precision,recall,and F-Score are presented.These results support the validity of our strategy since it performs the vast majority of prior studies in this domain.
