CYP7B1 – Congenital Bile Acid Synthesis Defect Type 3

Congenital bile acid synthesis defect type 3 is a rare autosomal recessive metabolic liver disease characterized by neonatal cholestasis, hepatic steatosis and conjugated hyperbilirubinemia. This association is supported by nine unrelated probands (including one newly described) all harboring biallelic CYP7B1 loss‐of‐function variants identified through molecular analyses; the most recent patient carried a homozygous single‐base duplication in exon 3 of CYP7B1 (PMID:35580280). Despite the cardinal hepatic phenotype, no segregation data beyond probands are reported.

Functional studies demonstrate that CYP7B1 is transcriptionally regulated by Sp1 binding at promoter GC boxes, and that its enzymatic activity in the alternative bile acid synthesis pathway is essential for oxysterol metabolism (PMID:11470525). Mouse Cyp7b1 knockouts surprisingly do not recapitulate human liver disease, indicating species‐specific compensation in bile acid synthesis (PMID:22111624). The mechanistic concordance of CYP7B1 haploinsufficiency in humans with neonatal cholestasis supports a Limited level of clinical validity. Genetic testing for CYP7B1 should be considered in infants presenting with unexplained cholestasis to facilitate early diagnosis and management.

References

• Gene • 2001 • Transcriptional regulation of human oxysterol 7 alpha-hydroxylase gene (CYP7B1) by Sp1. PMID:11470525
• Pediatric and developmental pathology • 2022 • Congenital Bile Acid Synthesis Defect Type 3 With Severe Neonatal Cholestasis. PMID:35580280
• The FEBS journal • 2012 • Cytochrome P450s in the synthesis of cholesterol and bile acids--from mouse models to human diseases. PMID:22111624

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