Rare variants in PKHD1 associated with Caroli syndrome: Two case reports.
Caroli disease
PKHD1 gene
genetic screening
uncertain significance variants
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
31
03
2022
received:
28
06
2021
accepted:
13
05
2022
pubmed:
19
6
2022
medline:
10
8
2022
entrez:
18
6
2022
Statut:
ppublish
Résumé
Caroli disease (CD, OMIM #600643) is a rare autosomal recessive disorder characterized by polycystic segmental dilatation of the intrahepatic bile ducts and extreme variability in age of onset and clinical manifestations. When congenital hepatic fibrosis is associated with the polycystic dilatation of the biliary tract, the condition is referred as Caroli syndrome. The disease is thought to be caused by pathogenic variants in the PKHD1 gene (OMIM *606702). We report the clinical, biochemical, and molecular characterization of three patients with a clinical suspicion of CS belonging to two different families. The genetic screening was performed using a target custom panel and sequencing was performed on Illumina platform. Genetic analysis revealed the presence of rare variants in the PKHD1 gene of the analyzed patients. In the first case, and his younger sister, two pathogenic variants (c.2702A>C and c.4870C>T) were found to be associated with a hepatic phenotype at clinical onset, followed by renal disease probably age-related; while in the second case, one pathogenic variant (c.5879C>G) and a complex allele with uncertain clinical significance [c.3407A>G; c.8345G>C; c.8606C>A] were found to be associated with a severe hepatic phenotype. The identification of the genetic causes of the disease and their relationship with the clinical phenotype could have a favorable impact on clinical management and complication prevention.
Sections du résumé
BACKGROUND
Caroli disease (CD, OMIM #600643) is a rare autosomal recessive disorder characterized by polycystic segmental dilatation of the intrahepatic bile ducts and extreme variability in age of onset and clinical manifestations. When congenital hepatic fibrosis is associated with the polycystic dilatation of the biliary tract, the condition is referred as Caroli syndrome. The disease is thought to be caused by pathogenic variants in the PKHD1 gene (OMIM *606702).
METHOD
We report the clinical, biochemical, and molecular characterization of three patients with a clinical suspicion of CS belonging to two different families. The genetic screening was performed using a target custom panel and sequencing was performed on Illumina platform.
RESULTS
Genetic analysis revealed the presence of rare variants in the PKHD1 gene of the analyzed patients. In the first case, and his younger sister, two pathogenic variants (c.2702A>C and c.4870C>T) were found to be associated with a hepatic phenotype at clinical onset, followed by renal disease probably age-related; while in the second case, one pathogenic variant (c.5879C>G) and a complex allele with uncertain clinical significance [c.3407A>G; c.8345G>C; c.8606C>A] were found to be associated with a severe hepatic phenotype.
CONCLUSION
The identification of the genetic causes of the disease and their relationship with the clinical phenotype could have a favorable impact on clinical management and complication prevention.
Identifiants
pubmed: 35715958
doi: 10.1002/mgg3.1998
pmc: PMC9356553
doi:
Substances chimiques
PKHD1 protein, human
0
Receptors, Cell Surface
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1998Informations de copyright
© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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