ABCB4 p.Thr175Val
| ClinVar: |
c.523A>G
,
p.Thr175Ala
D
, Pathogenic
|
| Predicted by SNAP2: | A: D (85%), C: D (85%), D: D (91%), E: D (91%), F: D (95%), G: D (85%), H: D (80%), I: D (95%), K: D (91%), L: D (91%), M: D (85%), N: D (59%), P: D (91%), Q: D (85%), R: D (95%), S: D (53%), V: D (95%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, V: D, W: D, Y: D, |
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[hide] MDR3 gene defect in adults with symptomatic intrah... Gastroenterology. 2001 May;120(6):1459-67. Rosmorduc O, Hermelin B, Poupon R
MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis.
Gastroenterology. 2001 May;120(6):1459-67., [PMID:11313316]
Abstract [show]
BACKGROUND & AIMS: Many studies indicate that gallstone susceptibility has genetic components. MDR3 is the phosphatidylcholine translocator across the hepatocyte canalicular membrane. Because phospholipids are a carrier and a solvent of cholesterol in hepatic bile, we hypothesized that a defect in the MDR3 gene could be the genetic basis for peculiar forms of cholesterol gallstone disease, in particular those associated with symptoms and cholestasis without evident common bile duct stone. METHODS: We studied 6 adult patients with a peculiar form of cholelithiasis. MDR3 gene sequence was determined by reverse-transcription polymerase chain reaction amplification of mononuclear cell RNAs followed by direct sequencing. Hepatic bile was analyzed in 2 patients. RESULTS: All patients shared the following features: at least 1 episode of biliary colic, pancreatitis, or cholangitis; biochemical evidence of chronic cholestasis; recurrence of symptoms after cholecystectomy; presence of echogenic material in the intrahepatic bile ducts; and prevention of recurrence by ursodeoxycholic acid therapy. Hepatic bile composition showed a high cholesterol/phospholipid ratio and cholesterol crystals. In all patients, we found MDR3 gene mutations involving a conserved amino acid region. CONCLUSIONS: These preliminary observations suggest that MDR3 gene mutations represent a genetic factor involved in this peculiar form of cholesterol gallstone disease in adults. They require further studies to assess the prevalence of MDR3 gene defects in symptomatic and silent cholesterol gallstone disease.
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No. Sentence Comment
155 Sequencing of amplified genomic DNA confirmed the homozygosity of patients 1 and 4 for mutation S320F, the heterozygosity of patients 2 and 3 for mutation 1327insA, the heterozygosity of patient 5 for mutation T175V, and the homozygosity of patient 6 for mutation P1161S.
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ABCB4 p.Thr175Val 11313316:155:210
status: NEW165 The early occurrence of gallstones in these patients might be consistent with an MDR3 dose effect similar to those observed for Jag1 gene expression in some patients with Alagille syndrome.18 A missense mutation changed an amino acid threonine into a valine (T175V; patient 5).
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ABCB4 p.Thr175Val 11313316:165:259
status: NEW[hide] Exome sequencing of a family with lone, autosomal ... BMC Genet. 2015 Feb 11;16:15. doi: 10.1186/s12863-015-0177-0. Maciag A, Villa F, Ferrario A, Spinelli CC, Carrizzo A, Malovini A, Torella A, Montenero C, Parisi A, Condorelli G, Vecchione C, Nigro V, Montenero AS, Puca AA
Exome sequencing of a family with lone, autosomal dominant atrial flutter identifies a rare variation in ABCB4 significantly enriched in cases.
BMC Genet. 2015 Feb 11;16:15. doi: 10.1186/s12863-015-0177-0., [PMID:25888430]
Abstract [show]
BACKGROUND: Lone atrial flutter (AFL) and atrial fibrillation (AF) are common and sometimes consequential cardiac conduction disorders with a strong heritability, as underlined by recent genome-wide association studies that identified genetic modifiers. Follow-up family-based genetic analysis also identified Mendelian transmission of disease alleles. Three affected members were exome-sequenced for the identification of potential causative mutations, which were subsequently validated by direct sequencing in the other 3 affected members. Taqman assay was then used to confirm the role of any mutation in an independent population of sporadic lone AFL/AF cases. RESULTS: The family cluster analysis provided evidence of genetic inheritance of AFL in the family via autosomal dominant transmission. The exome-sequencing of 3 family members identified 7 potential mutations: of these, rs58238559, a rare missense genetic variant in the ATP-binding cassette sub-family B, member 4 (ABCB4) gene was carried by all affected members. Further analysis of 82 subjects with sporadic lone AF, 63 subjects with sporadic lone AFL, and 673 controls revealed that the allele frequency for this variation was significantly higher in cases than in the controls (0.05 vs. 0.01; OR = 3.73; 95% CI = 1.16-11.49; P = 0.013). CONCLUSIONS: rs58238559 in ABCB4 is a rare missense variant with a significant effect on the development of AFL/AF.
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No. Sentence Comment
62 The rs58238559 single-nucleotide polymorphism (SNP) is located in the ABCB4 gene on chr7:87082273, and determines the nucleotide variation A599G (NM_000443.3) (Figure 2), producing the amino acid change Thr175Ala (NP_000434.1).
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ABCB4 p.Thr175Val 25888430:62:11
status: NEW63 Of note, a Thr175Val variation at the same position has been previously related to gallbladder disease in a sporadic case [18], while ABCB4 mutations are usually associated with familial forms of the disease [19].
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ABCB4 p.Thr175Val 25888430:63:11
status: NEW