Abstract:

Objective Using the next generation sequencing to explore the etiology of Chinese children with portal hypertension, which was hard to be diagnosed by routine examinations. Methods The whole exome sequencing and hepatic panel were used to explore the cause of four children with portal hypertension hospitalized in Jinshan Hospital of Fudan University from 2012 to March 2016. The clinical features were summarized retrospectively. Results The patients consisted of one male and three females, and their ages of onset ranged from 3.3 to 6.4 years with average age of 4.65 years. The main clinical features included upper gastrointestinal hemorrhage in three patients, splenomegaly in four patients, hepatomegaly in two patients, intra-hepatic bile duct dilation in one patient, elevation of serum alanine aminotransferase in two patients. Kidney lesions were detected by imaging in all patients, whereas both hepatic synthetic function and kidney function were tested to be normal. Finally, diverse compound heterozygous mutations were identified in PKHD1 gene in all patients by the next generation sequencing and confirmed by Sanger sequencing. The identified PKHD1 gene mutations included one nonsense mutation, one typical splicing site mutation, three deletion mutation induced frameshift mutations, and three rare missense mutations. c.8108-1G>A and c.4481delA p.N1494fs were identified in case 1, c.9568C>T p.Q3190X and c.2507T>C p.V836A were identified in case 2, c.9455delA p.N3152fs and c.847T>C p.F283L were identified in case 3, c.10315G>T p.D3439Y and c.3028-c.3039delGGAGAAGACCTCinsAGGT p.G1010fs were identified in case 4. All four children were diagnosed with autosomal recessive polycystic kidney disease. Conclusion Autosomal recessive polycystic kidney disease is an important cause of noncirrhotic portal hypertension in children, and the next generation sequencing is an effective method for diagnosis.