Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis

Area of Science:

• Genetics
• Hepatology
• Pediatric Gastroenterology

Background:

• Progressive familial intrahepatic cholestasis type 2 (PFIC) is a severe genetic liver disease.
• Mutations in the ABCB11 gene, encoding the bile salt export pump (BSEP), are the primary cause of PFIC type 2.

Observation:

• A Thai infant presented with progressive cholestatic jaundice from one month of age.
• Serum gamma-glutamyltransferase levels were normal.
• Liver immunohistochemistry showed absent BSEP expression at the canaliculi but normal multidrug resistance protein 3 (MRP3) expression.

Findings:

• Novel compound heterozygous mutations in ABCB11 were identified: a four-nucleotide deletion (c.90_93delGAAA) in exon 3 and a single-nucleotide insertion (c.249_250insT) in exon 5.
• These mutations were confirmed in the infant's parents.
• The identified mutations are predicted to result in truncated, non-functional BSEP proteins.

Implications:

• This case establishes a definitive diagnosis of PFIC type 2 in the infant.
• The findings highlight the importance of genetic analysis and BSEP immunostaining in diagnosing PFIC.
• Understanding these novel mutations contributes to the genetic landscape of PFIC type 2.