Evaluation of the Genetic Background of Patients with Niemann-Pick Disease

Background: Congenital liver disease refers to a group of heterogeneous diseases from a clinical genetic point of view. The most crucial features are hepatosplenomegaly and elevated liver enzymes. This study aims to identify genetic variants causing the disease in three Iranian families with congenital liver disease using molecular techniques. Methods: Patients were referred to Next Generation Genetic Polyclinic (NGGC) in Mashhad after confirmed congenital liver disease diagnosis by gastroenterologists. Following informed consent signed by participants, DNA was extracted from blood samples. Whole exome sequencing (WES) was performed for three probands. After the analysis of raw data, candidate variants were confirmed in the patients and their parents. Results: We have found the possible disease-causing variant as the c.1718G C variant (p. Trp573Ser) in the SMPD1 gene in the F-1 patient and c.1718G C (p. Trp573Ser) in the SMPD1 gene in the F-3 patient. Moreover, we have found the c.3175C T variant (p. Arg1059Ter) in the NPC1 gene in the F-2 patient. Conclusions: In this study, disease-causing variants were identified in three probands suspected of Niemann-Pick disease. Such results show the relatively high power of molecular techniques to assist clinicians with disease management, therapeutic strategies, and preventive options such as preimplantation genetic diagnosis and prenatal diagnosis.