BackgroundWilson disease (OMIM # 277900) is a autosomal recessive disorder characterized by accumulation of copper in liver and brain. The accumulation of copper resulting in oxidative stress and eventually cell death. The disease has an onset in a childhood and result in a significant neurological impairment or require lifelong treatment. Another serious consequence of the disease is the development of liver damage and acute liver failure leading to liver transplant. The disorder is caused by mutations in the ATP7B gene, encoding a P-type copper transporting ATPase.Case presentationWe performed genetic analysis of three unrelated patients from three different Vietnamese families. These patients had clinical features such as numbness of hands and feet, vomiting, insomnia, palsy, liver failure and Kayser–Fleischer (K–F) rings and were diagnosed with Wilson disease in the Human Genetics Department, Vietnam National Children’s Hospital. The entire coding region and adjacent splice sites of ATP7B gene were amplified and sequenced by Sanger method. Sequencing data were analyzed and compared with the ATP7B gene sequence published in Ensembl (ENSG00000123191) by using BioEdit software to detect mutations.ConclusionsIn this study, five mutations in the ATP7B gene were found. Among of these, three mutations were novel: c.750_751insG (p.His251Alafs*19) in exon 2, c.2604delC (p.Pro868Profs*5) in exon 11, and c.3077 T > A (p.Phe1026Tyr) in exon 14. Our results of the mutations associated with Wilson disease might facilitate the development of effective treatment plans.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0619-4) contains supplementary material, which is available to authorized users.

Objectives: To investigate the phytochemical constituents of Vietnamese Dalbergia oliveri and their inhibition of NO production. Methods: The ethyl acetate soluble fraction was subjected to column chromatography using silica gel and Sephadex LH-20 to isolate compounds. The chemical structures of isolated compounds were identified by nuclear magnetic resonance data and comparison with previously reported literature. The anti-inflammation effects of the isolated compounds on the lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells were measured using the Griess reaction. Results: Nine secondary metabolites (1−9) were isolated successfully from the heartwood of D. oliveri. The chemical structures of these compounds were identified as daidzein (1), formononetin (2), 3,7-dihydroxy-4′-methoxyflavone (3), liquiritigenin (4), 3′-methoxydaidzein (5), dalbergin (6), butin (7), sativanone (8), and isoliquiritigenin (9). This is the first time that compounds 1, 3, 5−8 have been isolated from D. oliveri. In the NO production inhibition, compounds 7 and 9 exhibited the most potent inhibitory activity, with IC50 values of 7.6 and 11.2 μM, respectively, followed by 3−6, with IC50 values from 19.6 to 28.7 μM. Conclusion: The results suggested that D. oliveri and its natural products might exert anti-inflammatory effects due to their NO-inhibiting actions.

Rationale: Hepatobiliary diseases such as biliary atresia (BA), Wilson disease, and progressive familial intrahepatic cholestasis are common causes of morbidity and mortality in young children. Affected patients progress rapidly to end-stage cirrhosis and require liver transplantation or die. Mutations in many genes have been identified to play an important role in the pathogenesis of hepatobiliary diseases. Patient concerns and diagnosis: In this study, we identified mutations in an 8-year-old girl who had severe liver failure. The patient was first diagnosed with BA at 2.5 months of age and has undergone Kasai surgery to connect the umbilical cord and jejunum. After that, the patient suddenly had unusual developments with symptoms of jaundice, acute liver failure with hemolysis. She was tested and diagnosed with Wilson disease. Interventions and outcomes: She was treated according to the regimen for a patient with Wilson disease but had abnormal progress leading to severe liver failure. Genetic analysis was performed by whole exome sequencing and Sanger sequencing methods. The genetic analysis revealed that the patient had a homozygous mutation (p.Gly17Glyfs77∗) in the KRT18 gene, a double heterozygous mutation (p.Ser105∗ and p.Pro992Leu) in the ATP7B gene, and a homozygous variant (p.Val444Ala) in the ABCB11 gene. In silico prediction of mutations indicated that these mutations are the cause of the severe liver failure in the patient. Lesson: This is a rare clinical case of a BA patient combined with Wilson disease. Our results suggested that whole exome sequencing is an effective diagnostic tool and emphasizes the importance of early diagnosis and appropriate management to save lives and prevent serious complications in the patient.