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Background: Hepatorenal fibrocystic diseases (HRFCDs) are a group of monogenic disorders characterized by developmental abnormalities involving the liver and kidney. In this study, we performed genotype and phenotype analyses of children with HRFCDs to determine the distribution of underlying diseases. Methods: A total of 36 children with HRFCDs were recruited, with genetic tests being performed in 22 patients and 14 patients diagnosed clinically as having autosomal recessive polycystic kidney disease (ARPKD). Results: In children with HRFCDs, ARPKD was the most common disease, found in 16/36 (44.4 %), followed by nephronophthisis 13 (NPHP13) in 11/36 (30.6 %) and Meckel-Gruber syndrome type 3 (MKS3) in 4/36 (11.1 %). Renal function deteriorated faster in children with NPHP13. The main hepatic pathology was Caroli disease in the NPHP13 patients, while most other patients had Caroli syndrome or congenital hepatic fibrosis. Of note, three of four MKS3 patients had an accompanying choledochal cyst. No ARPKD patient had other organ involvement, while several NPHP13 patients had ocular and/or neurodevelopmental involvement. In contrast, all MKS3 patients had severe ocular and neurodevelopmental involvement. Conclusions: NPHP13 is a major disease in the HRFCD category, and thorough evaluation of its clinical features, including kidney, liver and other organ involvement, may aid in the differential diagnosis of HRFCD. [ABSTRACT FROM AUTHOR]

Background: Nephronophthisis 13 (NPHP 13) is associated with mutations in the WDR19 gene, which encodes for a protein in the intraflagellar transport complex. Herein, we describe six additional cases accompanied by Caroli syndrome or disease. Methods: Targeted exome sequencing covering 96 ciliopathy-related genes was performed for 48 unrelated Korean patients with a clinical suspicion of NPHP. Mutations were confirmed by Sanger sequencing. We evaluated the expression of WDR19 in the biopsied kidney by immunohistochemistry in patients and controls. Results: We detected three (3/48, 6.3 %) unrelated index cases with WDR19 mutations. One of the cases involved two siblings with the same mutation. Later, we detected an additional index case with a similar phenotype of kidney and liver involvement by Sanger sequencing of WDR19. The p.R1178Q mutation was common in all patients. All of the six affected patients from four families progressed to chronic kidney disease. Of note, all six patients had Caroli syndrome or disease. Immunohistochemistry for WDR19 showed localized expression along the luminal borders of the renal tubular epithelium in controls, whereas it showed diffuse cytoplasmic staining in the affected patients. Conclusions: Caroli disease is a major extra-renal phenotype associated with mutations in WDR19 in the Korean population. In this study, we visually validated the expression pattern of mutant WDR19 protein in the kidneys of NPHP 13 patients. More data are needed to identify the true frequency of p.R1178Q. Functional studies including transfection assay will provide solid grounds for the pathogenicity of each mutation. [ABSTRACT FROM AUTHOR]