Novel VPS33B mutations of G514S gene cause an arthrogryposis, renal dysfunction and cholestasis syndrome

Introduction: Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare multisystem disorder first described in 1979 and recently attributed to mutation in VPS33B, whose product acts in intracellular trafficking. It shows wide clinical variability. The characteristic features of ARC core phenotype include arthrogryposis, spillage of various substances in the urine, and conjugated hyperbilirubinemia. In some patients, these features are sometimes accompanied by different manifestations, such as ichthyosis, central nervous system malformation, deafness, and platelet abnormalities. Many patients with different associations of cholestasis, renal tubular acidosis, and dysmorphic morphology may be underdiagnosed. Case Report: We assessed the clinical characteristics of patients and investigated the VPS33B mutation in the gene G514S in a Turkish patient with ARC syndrome. We reported one Turkish patient with ARC syndrome, along with the presentations of renal tubular dysfunction, cholestasis, arthrogryposis, VPS33B Mutations in the gene G514S. Conclusion: This case shows that the variability of different manifestations of ARC syndrome is well described. However, the presence of the mutations VPS33B in the gene G514S has not been reported before. Our findings advance the knowledge of the molecular pathways determining cell polarity and provide new evidence on the role of intracellular trafficking proteins in regulation of epithelial polarization. Further, the fundamental defects in growth and differentiation of epithelial tissues observed in ARC and in knockdown cell lines emphasize the importance of the VPS33B pathway for organ development and function. We found a novel mutation in a Turkish patient with ARC syndrome. (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 7 No. 4, April 2016. ISSN – [0976-3198] Int J Case Rep Imag 2016;7(4):216–220. www.ijcasereportsandimages.com Conkar et al. 216 CASE REPORT OPEN ACCESS Novel VPS33B mutations of G514S gene cause an arthrogryposis, renal dysfunction and cholestasis syndrome Seçil Conkar, Ebru Yılmaz, Sevgi Mir, Afig Berdeli