Newly Described Mutations of the UNC45A Gene in Infants with Jaundice and Pruritus.

BACKGROUND: Cholestatic liver disease is an important cause of morbidity and mortality and a leading indication for liver transplantation in children. These include diseases, such as biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, sclerosing cholangitis, bile acid synthesis defects, and many others. CASE PRESENTATION: NGS was used as a diagnostic tool to identify the genetic cause in the patient with cholestatic syndrome and to figure out and describe what mutation will be found. In the present observation, the cholestasis syndrome with low GGT activity and intense pruritus was the leading symptom of the patient. The examination also revealed other characteristic features of osteo- oto-hepato-enteric syndrome. The patient had facial features that mimicked Alagille syndrome, which complicated the diagnostic search. Moreover, the genetic test revealed two new pathogenic variants in the UNC45A gene. CONCLUSION: This clinical observation demonstrates the importance of a multidisciplinary approach in the diagnosis of rare genetic diseases and using WES, which can accelerate the diagnosis compared with outdated gene panels.

Molecular diagnosis of tuberous sclerosis complex in fetuses and infants: an institutional case series.

OBJECTIVE: We describe the clinical and genetic characteristics of fetuses and infants diagnosed with tuberous sclerosis complex (TSC) in our centre, prenatally or neonatally, for a better understanding of the benefits of early screening. METHODS: In this retrospective study, we analysed the data on one fetus and nine infants with a definitive TSC diagnosis by genetic criteria (five patients carrying TSC1 variants and 5 patients carrying TSC2 variants). We explored the differences between phenotypes of patients carrying TSC1 and TSC2 pathogenic variants. RESULTS: The most common initial presenting features of TSC were cardiac rhabdomyomas (CRs) that were observed in nine out of ten patients. The most common postnatal features, besides CR, were presented with subependymal nodules-in five patients, and hypomelanotic macules-in four patients. In total, 10 variants causing TSC were detected in this study, including 5 novel variants. We demonstrated that patients with TSC2 variants had earlier onset and more severe clinical manifestations compared with patients carrying TSC1 variants. CONCLUSION: Early diagnosis of TSC improves genetic counselling and perinatal management.