-Related Ciliopathy: Report of Six Polish Patients, Novel Variant, and Literature Review of Reported Cases.

INTRODUCTION

The increasing usage of NGS technology has enabled the discovery of new causal genes in ciliopathies, including the gene. The aim of our study was to present the clinical, pathological and molecular report of six patients (from three unrelated families) with biallelic pathogenic variants. A detailed overview of the reported patients with -related disease was provided.

MATERIAL AND METHODS

A retrospective chart review of the clinical, biochemical, pathological (liver histology) and molecular features of the study group was performed. The database PubMed (MEDLINE) was searched for relevant studies.

RESULTS

All the patients presented with cholestatic jaundice and elevated GGT; the mean age was 2 months. The initial liver biopsy was performed in four children at a mean age of 3 months (age range: 2-5 months). In all of them, features of cholestasis, portal fibrosis and mild portal inflammation were observed; in three of them ductular proliferation was observed. One patient had undergone liver transplantation (LTx) at 8 years of age. At hepatectomy, a biliary-pattern cirrhosis was observed. Only one patient presented with features of renal disease. Whole exome sequencing was performed in all patients at the last follow-up visit (mean age 10 years). Three different variants (one novel) in the gene were identified in the study group. With our six patients, a total of 34 patients with -related hepatic ciliopathy were identified. The main clinical presentation of -related ciliopathy was liver disease in the form of neonatal sclerosing cholangitis. The predominance of early and severe liver disease associated with no or mildly expressed kidney involvement was observed.

CONCLUSIONS

Our findings expand the molecular spectrum of pathogenic variants, provide a more accurate picture of the phenotypic expression associated with molecular changes in this gene and confirm a loss of functional behaviour as the mechanism of disease.