[Clinical and genetic analysis of an infant with progressive familial intrahepatic cholestasis type II]

Area of Science:

• Genetics
• Pediatric Hepatology
• Molecular Biology

Background:

• Progressive Familial Intrahepatic Cholestasis type II (PFIC-2) is an autosomal recessive liver disorder.
• It results from biallelic variants in the ABCB11 gene, which encodes the bile salt export pump (BSEP).
• Impaired BSEP function leads to cholestasis and liver damage.

Purpose of the Study:

• To report the clinical and laboratory findings of a pediatric patient diagnosed with PFIC-2.
• To identify the genetic variants responsible for PFIC-2 in this patient.
• To characterize a potentially novel pathogenic variant in the ABCB11 gene.

Main Methods:

• Clinical assessment of a 2.4-month-old male infant presenting with jaundice and hepatomegaly.
• Biochemical analysis of serum liver function tests, including bilirubin and γ-glutamyl transpeptidase (GGT).
• Next-generation sequencing (NGS) of the ABCB11 gene to identify causative variants.
• Bioinformatic tools were used to predict the pathogenicity of identified variants.

Main Results:

• The patient exhibited classic PFIC-2 symptoms: jaundice and hepatomegaly.
• Elevated serum total bilirubin, direct bilirubin, and total bile acids were observed.
• Notably, serum GGT levels were within the normal range.
• NGS identified two missense variants in the ABCB11 gene: c.1493T>C (p.Ile498Thr) and a novel variant c.1502T>G (p.Val501Gly).
• The novel p.Val501Gly variant was predicted to be pathogenic and affects a highly conserved residue.

Conclusions:

• This case highlights the clinical presentation of PFIC-2 in an infant, emphasizing the importance of considering genetic testing in cases of unexplained cholestasis.
• The identification of two ABCB11 variants, including a novel pathogenic mutation, confirms the diagnosis of PFIC-2.
• The findings contribute to the understanding of genotype-phenotype correlations in PFIC-2 and the functional impact of ABCB11 variants.