RGD Reference Report - ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones. - Rat Genome Database

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ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones.

Authors: Jirsa, Milan  Bronský, Jiří  Dvořáková, Lenka  Šperl, Jan  Šmajstrla, Vít  Horák, Jiří  Nevoral, Jiří  Hřebíček, Martin 
Citation: Jirsa M, etal., World J Gastroenterol. 2014 May 21;20(19):5867-74. doi: 10.3748/wjg.v20.i19.5867.
RGD ID: 14694981
Pubmed: PMID:24914347   (View Abstract at PubMed)
PMCID: PMC4024796   (View Article at PubMed Central)
DOI: DOI:10.3748/wjg.v20.i19.5867   (Journal Full-text)


AIM: To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.
METHODS: Mutational analysis of ABCB4, screening for copy number variations by multiplex ligation-dependent probe amplification, genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome (LPAC, OMIM #600803) and in 5 young females with suspected LPAC and their families (5 probands, 15 additional family members). The probands came to medical attention for contraceptive-associated intrahepatic cholestasis.
RESULTS: A possibly pathogenic variant of ABCB4 was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4. Among these 16, however, none developed gallstones in childhood. In 5 index patients, all young females carrying at least one pathogenic mutation in one allele of ABCB4, manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives. Variants ABCB11 c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.
CONCLUSION: Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied to pediatric patients with idiopathic gallstones. Sexual immaturity even prevents manifestation of LPAC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Gallbladder Disease 1  IAGP 14694981DNA:missense mutation:cds:p.Thr175Ala(human)RGD 
Gallbladder Disease 1  ISOABCB4 (Homo sapiens)14694981; 14694981DNA:missense mutation:cds:p.Thr175Ala(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcb4  (ATP binding cassette subfamily B member 4)

Genes (Mus musculus)
Abcb4  (ATP-binding cassette, sub-family B member 4)

Genes (Homo sapiens)
ABCB4  (ATP binding cassette subfamily B member 4)


Additional Information