MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis

Rosmorduc, Olivier; Hermelin, B.; Poupon, Raoul

doi:10.1053/gast.2001.23947

Cited by 315 publications

(243 citation statements)

References 33 publications

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“…An additional application of the chip is as an investigative tool to study the role of synonymous and non-synonymous polymorphisms of individual genes, or of heterozygous polymorphisms in functionally related genes, in phenotype determination of children and adults with chronic cholestasis, intrahepatic cholestasis of pregnancy, and gallstone formation associated with mutations in ABCB4. 43,44 One specific disease that may benefit from such investigative approach is biliary atresia, in which the systematic analysis of all five genes may provide insight into the potential role of genetic variations in long-term survival with the native liver. For all of these settings, the current version of the Jaundice Chip offers a real opportunity to translate laboratory discoveries into a tool that may simplify the diagnostic algorithm at the bedside, and facilitate the design of treatment protocols that take into account the genetic makeup of the patient.…”

Section: Discussionmentioning

confidence: 99%

Novel Resequencing Chip Customized to Diagnose Mutations in Patients With Inherited Syndromes of Intrahepatic Cholestasis

et al. 2007

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Background and Aims-Inherited syndromes of intrahepatic cholestasis commonly result from mutations in the genes SERPINA1 (α1-antitrypsin deficiency), JAG1 (Alagille syndrome), ATP8B1 (Progressive Familial Intrahepatic Cholestasis type 1/PFIC1), ABCB11 (PFIC2), and ABCB4 (PFIC3). However, the large gene sizes and lack of mutational hotspots make it difficult to survey for disease-causing mutations in clinical practice. Here, we aimed to develop a technological tool that reads out the nucleotide sequence of these genes rapidly and accurately.

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Section: Discussionmentioning

confidence: 99%

Novel Resequencing Chip Customized to Diagnose Mutations in Patients With Inherited Syndromes of Intrahepatic Cholestasis

et al. 2007

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“…No sucede lo mismo en aquellos pacientes en que la mutación se manifiesta por una proteína truncada, donde no hay actividad transportadora de fosfolípidos, permitiendo así que la acción detergente de los ácidos biliares dañe el epitelio de los conductos biliares; en esta situación, la respuesta al ácido ursodeoxicólico es nula o mínima evolucionan con daño hepático progresivo hacia una cirrosis. Las mutaciones heterocigotas de MDR3 son causantes de otras patologías como la colestasia del embarazo y de litiasis de la vesícula biliar 12,13 .…”

Section: Discussionunclassified

Colestasia Intrahepática Familiar Progresiva Tipo 3: Presentación de Casos Clínicos y Actualización de Tema

2009

Rev. chil. pediatr.

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Familial Intrahepatic Cholestasis (FIC) includes a heterogeneous group of recessive autosomic alterations characterized by hepatocellular cholestasis secondary to the interruption of the normal process of synthesis of bilis. Objective: A description of FIC in 3 of 5 children of an index family. Clinical case: a 5 y.o. child with hepatosplenomegaly increased serum hepatic enzymes and biliary acids. Abdominal echography showed alterations compatible with hepatic fibrosis. Biopsy showed bridge fibrosis, duct proliferation, minimal chronic cholestasis. These findings were compatible with a phenotype FIC-3 with elevate levels of Gamma-glutamyl transferase. A mutation of MDR3 gene is responsible for the absence of biliary phospholipids, allowing a detergent effect of biliary acids upon the duct epithelium, developing cholangitis, fibrosis and later cirrhosis. Among four brothers, the mutation was found in two twin sisters. Three affected brothers were treated with ursodeoxicolic acid, 30 mg/Kg. Excellent results were obtained in the twin girls not in the index boy. The clinical expression of this illness is variable, and an elevation of aminotransferase must call attention to this possibility. Early diagnostic and treatment could avoid the development of hepatic damage and cirrhosis.

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“…Each patient had symptom onset prior to age 40, cholesterol gallstones and intrahepatic sludge/microlithiasis (as seen by hyperechoic foci on radiologic exams) and recurrent biliary symptoms even after cholecystectomy. The term "LPAC (Low Phospholipid Associated Cholelithiasis) Syndrome" was derived from this study 28 . Post-cholecystectomy biliary symptoms may be due to intrahepatic cholesterol deposits and bile duct inflammation, rather than detectable stones 29 .…”

Section: Clinical Presentationmentioning

confidence: 99%

“…• In LPAC syndrome, ursodeoxycholic acid (UDCA) may improve biliary symptoms even before intrahepatic stones resolve 28,35 .…”

Section: Treatmentmentioning

confidence: 99%

The multiple facets of ABCB4 (MDR3) deficiency

Sundaram

Sokol²

2007

Curr Treat Options Gastro

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MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis

Cited by 315 publications

References 33 publications

Novel Resequencing Chip Customized to Diagnose Mutations in Patients With Inherited Syndromes of Intrahepatic Cholestasis

Novel Resequencing Chip Customized to Diagnose Mutations in Patients With Inherited Syndromes of Intrahepatic Cholestasis

Colestasia Intrahepática Familiar Progresiva Tipo 3: Presentación de Casos Clínicos y Actualización de Tema

The multiple facets of ABCB4 (MDR3) deficiency

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