BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused ...BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis.CASE SUMMARY We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy.Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury.Exon analyses of the whole genome from the patient’s peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene.Bone marrow biopsy tissues,renal puncture examination,and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis,which resulted in cirrhosis.Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment.Following treatment,the patient demonstrated significant improvement.Urinary protein became negative,peripheral blood-free light chain and urine-free light chain levels returned to normal,and the electrocardiogram showed no abnormalities.Additionally,the patient’s lower limb numbness resolved,and her condition remained stable.CONCLUSION This report presents the diagnosis and treatment of liver cirrhosis,a rare disease that is easily misdiagnosed or missed.展开更多
The ABCB4 gene,also called MDR3,encodes the MDR3 protein which is localized to the hepatocyte canalicular membrane and is demonstrated to be a phosphatidylcholine translocase.The recent study showed that ABCB4 deficie...The ABCB4 gene,also called MDR3,encodes the MDR3 protein which is localized to the hepatocyte canalicular membrane and is demonstrated to be a phosphatidylcholine translocase.The recent study showed that ABCB4 deficiency was associated with several cholestatic disorders,but the pathogenesis is not clear.This review highlights recent advances in the structure and function of ABCB4 gene,and the relationship between ABCB4 gene and cholestatic diseases.展开更多
BACKGROUND Mutations that occur in the ABCB4 gene,which encodes multidrug-resistant protein 3,underlie the occurrence of progressive familial intrahepatic cholestasis type 3(PFIC3).Clinical signs of intrahepatic chole...BACKGROUND Mutations that occur in the ABCB4 gene,which encodes multidrug-resistant protein 3,underlie the occurrence of progressive familial intrahepatic cholestasis type 3(PFIC3).Clinical signs of intrahepatic cholestasis due to gene mutations typically first appear during infancy or childhood.Reports of PFIC3 occurring in adults are rare.CASE SUMMARY This is a case study of a 32-year-old infertile female Chinese patient with a 15-year history of recurrent abnormal liver function.Her primary clinical signs were elevated levels of alkaline phosphatase andγ-glutamyl transpeptidase.Other possible reasons for liver dysfunction were eliminated in this patient,resulting in a diagnosis of PFIC3.The diagnosis was confirmed using gene detection and histological analyses.Assessments using genetic sequencing analysis indicated the presence of two novel heterozygous mutations in the ABCB4 gene,namely,a 2950C>T;p.A984V mutation(exon 24)and a 667A>G;p.I223V mutation(exon 7).After receiving ursodeoxycholic acid(UDCA)treatment,the patient's liver function indices improved,and she successfully became pregnant by in vitro fertilization.However,the patient developed intrahepatic cholestasis of pregnancy in the first trimester.Fortunately,treatment with UDCA was safe and effective.CONCLUSION These novel ABCB4 heterozygous mutations have a variety of clinical phenotypes.Continued follow-up is essential for a comprehensive understanding of PFIC3.展开更多
目的探讨妊娠期肝内胆汁淤积症(ICP)孕妇胎盘ABCB4基因表达水平,分析其与妊娠结局的关系。方法选取2017年5月至2020年11月于延安大学咸阳医院分娩的ICP孕妇98例纳入ICP组,并将ICP组孕妇按照血清总胆汁酸水平将<40 mol/L者纳入轻度组(...目的探讨妊娠期肝内胆汁淤积症(ICP)孕妇胎盘ABCB4基因表达水平,分析其与妊娠结局的关系。方法选取2017年5月至2020年11月于延安大学咸阳医院分娩的ICP孕妇98例纳入ICP组,并将ICP组孕妇按照血清总胆汁酸水平将<40 mol/L者纳入轻度组(n=61),≥40 mol/L者纳入重度组(n=37),另选取健康孕妇50例纳入对照组,收集纳入对象娩出的胎盘绒毛组织,通过RT-PCR和免疫组化法分别检测胎盘组织ABCB4 mRNA和ABCB4蛋白表达水平,对比不同组别胎盘绒毛组织中ABCB4基因表达的差异,通过Logistic回归分析其与ICP孕妇妊娠结局的关系。结果ICP组胎盘组织中ABCB4 m RNA表达水平为7.59±2.01,明显低于对照组的26.91±3.45,ABCB4蛋白阳性表达率为58.16%,明显低于对照组的96.00%,差异均有统计学意义(P<0.05);重度组胎盘组织中ABCB4 m RNA表达水平6.57±1.29,明显低于轻度组的8.21±1.43,ABCB4蛋白阳性表达率为43.24%,明显低于轻度组的67.21%,差异均有统计学意义(P<0.05);ICP组孕妇中46例出现不良妊娠结局,发生率为46.94%;ICP组孕妇羊水污染、胎儿窘迫、早产、新生儿窒息、围生儿死亡发生率分别为25.51%、23.47%、28.57%、17.35%、8.16%,明显高于对照组的8.00%、8.00%、4.00%、4.00%、0,差异均有统计学意义(P<0.05);Logisitic回归分析结果显示,高龄、发病时孕周≤34周、疾病程度高、ABCB4蛋白阴性表达、ABCB4 m RNA低表达是ICP孕妇发生不良妊娠结局的独立危险因素(P<0.05)。结论ICP孕妇胎盘组织ABCB4基因呈现低表达状态,胎盘组织ABCB4基因表达水平与妊娠结局关系密切,ABCB4基因表达水平下降可增加不良妊娠结局风险。展开更多
Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is uncle...Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.展开更多
目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显...目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子14和23,再对PCR产物进行DNA测序分析。结果所有ICP患者及对照组外周血DNA经PCR均扩增出目的片段,外显子14和23均未发现有突变。结论云南临沧佤族、傣族ICP的发生可能与MDR3基因外显子14和23突变无关。展开更多
基金Supported by The Department of Science and Technology of Guizhou Province,No.[2020]1Y299National Natural Science Foundation of China,No.82060123+2 种基金National Health Commission of Guizhou Province,No.gzwjk2019-1-082Doctor Start Fund of Affiliated Hospital of Guizhou Medical University,No.gyfybsky-2021-28National Natural Cultivation Fund of Affiliated Hospital of Guizhou Medical University,No.Ⅰ-2020-12.
文摘BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis.CASE SUMMARY We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy.Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury.Exon analyses of the whole genome from the patient’s peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene.Bone marrow biopsy tissues,renal puncture examination,and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis,which resulted in cirrhosis.Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment.Following treatment,the patient demonstrated significant improvement.Urinary protein became negative,peripheral blood-free light chain and urine-free light chain levels returned to normal,and the electrocardiogram showed no abnormalities.Additionally,the patient’s lower limb numbness resolved,and her condition remained stable.CONCLUSION This report presents the diagnosis and treatment of liver cirrhosis,a rare disease that is easily misdiagnosed or missed.
文摘The ABCB4 gene,also called MDR3,encodes the MDR3 protein which is localized to the hepatocyte canalicular membrane and is demonstrated to be a phosphatidylcholine translocase.The recent study showed that ABCB4 deficiency was associated with several cholestatic disorders,but the pathogenesis is not clear.This review highlights recent advances in the structure and function of ABCB4 gene,and the relationship between ABCB4 gene and cholestatic diseases.
基金Supported by Natural Science Foundation of Gansu Province,No.21JR7RA410.
文摘BACKGROUND Mutations that occur in the ABCB4 gene,which encodes multidrug-resistant protein 3,underlie the occurrence of progressive familial intrahepatic cholestasis type 3(PFIC3).Clinical signs of intrahepatic cholestasis due to gene mutations typically first appear during infancy or childhood.Reports of PFIC3 occurring in adults are rare.CASE SUMMARY This is a case study of a 32-year-old infertile female Chinese patient with a 15-year history of recurrent abnormal liver function.Her primary clinical signs were elevated levels of alkaline phosphatase andγ-glutamyl transpeptidase.Other possible reasons for liver dysfunction were eliminated in this patient,resulting in a diagnosis of PFIC3.The diagnosis was confirmed using gene detection and histological analyses.Assessments using genetic sequencing analysis indicated the presence of two novel heterozygous mutations in the ABCB4 gene,namely,a 2950C>T;p.A984V mutation(exon 24)and a 667A>G;p.I223V mutation(exon 7).After receiving ursodeoxycholic acid(UDCA)treatment,the patient's liver function indices improved,and she successfully became pregnant by in vitro fertilization.However,the patient developed intrahepatic cholestasis of pregnancy in the first trimester.Fortunately,treatment with UDCA was safe and effective.CONCLUSION These novel ABCB4 heterozygous mutations have a variety of clinical phenotypes.Continued follow-up is essential for a comprehensive understanding of PFIC3.
文摘目的探讨妊娠期肝内胆汁淤积症(ICP)孕妇胎盘ABCB4基因表达水平,分析其与妊娠结局的关系。方法选取2017年5月至2020年11月于延安大学咸阳医院分娩的ICP孕妇98例纳入ICP组,并将ICP组孕妇按照血清总胆汁酸水平将<40 mol/L者纳入轻度组(n=61),≥40 mol/L者纳入重度组(n=37),另选取健康孕妇50例纳入对照组,收集纳入对象娩出的胎盘绒毛组织,通过RT-PCR和免疫组化法分别检测胎盘组织ABCB4 mRNA和ABCB4蛋白表达水平,对比不同组别胎盘绒毛组织中ABCB4基因表达的差异,通过Logistic回归分析其与ICP孕妇妊娠结局的关系。结果ICP组胎盘组织中ABCB4 m RNA表达水平为7.59±2.01,明显低于对照组的26.91±3.45,ABCB4蛋白阳性表达率为58.16%,明显低于对照组的96.00%,差异均有统计学意义(P<0.05);重度组胎盘组织中ABCB4 m RNA表达水平6.57±1.29,明显低于轻度组的8.21±1.43,ABCB4蛋白阳性表达率为43.24%,明显低于轻度组的67.21%,差异均有统计学意义(P<0.05);ICP组孕妇中46例出现不良妊娠结局,发生率为46.94%;ICP组孕妇羊水污染、胎儿窘迫、早产、新生儿窒息、围生儿死亡发生率分别为25.51%、23.47%、28.57%、17.35%、8.16%,明显高于对照组的8.00%、8.00%、4.00%、4.00%、0,差异均有统计学意义(P<0.05);Logisitic回归分析结果显示,高龄、发病时孕周≤34周、疾病程度高、ABCB4蛋白阴性表达、ABCB4 m RNA低表达是ICP孕妇发生不良妊娠结局的独立危险因素(P<0.05)。结论ICP孕妇胎盘组织ABCB4基因呈现低表达状态,胎盘组织ABCB4基因表达水平与妊娠结局关系密切,ABCB4基因表达水平下降可增加不良妊娠结局风险。
文摘Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.
文摘目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子14和23,再对PCR产物进行DNA测序分析。结果所有ICP患者及对照组外周血DNA经PCR均扩增出目的片段,外显子14和23均未发现有突变。结论云南临沧佤族、傣族ICP的发生可能与MDR3基因外显子14和23突变无关。
