Dataset Information

Rare variants in PKHD1 associated with Caroli syndrome: Two case reports.

ABSTRACT:

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.

SUBMITTER: Giacobbe C

PROVIDER: S-EPMC9356553 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Rare variants in PKHD1 associated with Caroli syndrome: Two case reports.

Giacobbe Carola C Di Dato Fabiola F Palma Daniela D Amitrano Michele M Iorio Raffaele R Fortunato Giuliana G

Molecular genetics & genomic medicine 20220617 8

<h4>Background</h4>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).<h4>Method</h4>We rep ...[more]

PMID: 35715958

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Project description:BackgroundSusac syndrome is an immune-mediated, ischemia-producing, occlusive microvascular endotheliopathy that threatens the brain, retina, and inner ear. There is a need for disease assessment tools that can help clinicians and patients to more easily, accurately, and uniformly track the clinical course and outcome of Susac syndrome. Ideally, such tools should simultaneously facilitate the clinical care and study of Susac syndrome and improve the value of future case reports. To meet this need, two novel clinical assessment tools were developed: the Susac Symptoms Form and the Susac Disease Damage Score. The former is a comprehensive self-report form that is completed by patients/families to serially document the clinical status of a patient. The latter documents the extent of damage perceived by individual patients/families and their physicians. Both forms were initially trialed with two particularly representative and instructive patients. The results of this trial are shared in this report.Case presentationPatient 1 is a 21-year-old Caucasian female who presented with an acute onset of headache, paresthesias, cognitive dysfunction, and emotional lability. Patient 2 is a 14-year-old Caucasian female who presented with an acute onset of headache, cognitive dysfunction, urinary incontinence, ataxia, and personality change. Both patients fulfilled criteria for a definite diagnosis of Susac syndrome: both eventually developed brain, retinal, and inner ear involvement, and both had typical "snowball lesions" on magnetic resonance imaging. The Susac Symptoms Form documented initial improvement in both patients, was sufficiently sensitive in detecting a subsequent relapse in the second patient, and succinctly documented the long-term clinical course in both patients. The Disease Damage Score documented minimal disease damage in the first patient and more significant damage in the second.ConclusionsThe Susac Symptoms Form and the Disease Damage Score are useful disease assessment tools, both for clinical care and research purposes. Their use could enhance the value of future case reports on Susac syndrome and could improve opportunities to learn from a series of such reports.

Dataset Information

Rare variants in PKHD1 associated with Caroli syndrome: Two case reports.

Background

Method

Results

Conclusion

Publications

Rare variants in PKHD1 associated with Caroli syndrome: Two case reports.

Similar Datasets

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