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Novel PLEC variants associated with infantile cholestasis
Phawin Kor-Anantakul1,2, Huey-Ling Chen3, Ya-Hui Chen3
1Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Clinical Genetics
|August 21, 2024
Summary
Plectin mutations cause cholestatic jaundice in infants. Exome sequencing identified novel PLEC gene variants, confirming plectin
Area of Science:
- Genetics
- Molecular Biology
- Hepatology
Background:
- Plectin (PLEC) is an intermediate filament cytoskeletal linker.
- Plectin mutations have been linked to progressive familial intrahepatic cholestasis.
- Infantile cholestasis presents a diagnostic challenge.
Purpose of the Study:
- To investigate the role of plectin in infantile cholestatic jaundice.
- To identify genetic variants associated with plectin-related cholestasis.
- To evaluate exome sequencing for diagnosing genetic causes of infantile cholestasis.
Main Methods:
- Trio exome sequencing was performed on two unrelated infants with cholestatic jaundice.
- Genetic variants in the PLEC gene were identified.
- Immunofluorescence staining of liver biopsy samples was conducted to assess plectin and cytokeratin 8 localization.
Main Results:
- Two infants presented with cholestatic jaundice due to compound heterozygous variants in the PLEC gene.
- Novel PLEC variants, including c.71-11768C>T, c.4331G>T, c.592C>T, and c.4322G>A, were identified.
- Liver samples showed reduced plectin and cytokeratin 8 colocalization in hepatocytes.
Conclusions:
- Plectin plays a role in cholestasis, with mutations leading to infantile cholestatic jaundice.
- Novel PLEC gene variants are associated with this condition.
- Exome sequencing is an effective diagnostic tool for identifying genetic causes of infantile cholestasis.
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