RESUMO
Objective@#To explore the relationship between genotype and phenotype of ABCB11 deficiency.@*Methods@#Clinical data of two siblings with ABCB11 deficiency were retrospectively analyzed. Related literature from PubMed, CNKI and Wangfang databases was reviewed to date (up to August 2017) with 'ABCB11 gene’ or 'bile salt export pump’, 'cholestasis’ and 'child’ as key words.@*Results@#The patients were siblings. Both of them presented as jaundice, pruritus and hepatosplenomegaly since 3 days after birth. Significant laboratory findings on admission of the older sister included high total bilirubin, 170 µmol/L;conjugated bilirubin, 115.8 µmol/L;alanine aminotransferase, 168 U/L;total bile acid 186.3 µmol/L and normal gamma-glutamyl transpeptidase. While routine laboratory data of the younger brother were as follows: total bilirubin, 148.8 µmol/L;conjugated bilirubin, 96.3 µmol/L;alanine aminotransferase, 232.8 U/L;total bile acid 226 µmol/L, and normal gamma-glutamyl transpeptidase.Both received ursodeoxycholic acid and fat-soluble vitamins. Liver pathology of the younger brother showed giant hepatocytes with ballooning degeneration, focal necrosis and intrahepatic cholestasis. Both the patients harbor the same compound heterozygous mutations in ABCB11 gene, c.145C>T (p.Q49X) and c.1510G>A (p.E504K). The sister is 9 years old now, with normal liver function. Jaundice faded around 3 months after birth, pruritus relieved at age 5, and medications was stopped since then. The brother progressed to liver failure after an operation on perianal abscess when he was 8-month-old, and received living-related liver transplantation when he was 9 month and 20 days old (from his mother). Now he is 1 year and 5 months old, with normal liver function. Both are under our follow-up. Literature review revealed 18 ABCB11 deficiency patients from 7 families who had apparent different prognoses, within each family the siblings had the same ABCB11 gene mutation. Seven cases relieved after ursodeoxycholic acid therapy and/or partial external biliary diversion, 5 received orthotopic liver transplantation, 2 developed hepatocellular carcinoma and 4 cases died in childhood.@*Conclusions@#The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype, even in siblings. Patients should be managed in individualized maner.
RESUMO
In China, several subtype avian influenza viruses consistently circulate in poultry. Numerous studies have focused on the evolution of the hemagglutinin gene; however, studies on the evolution of the matrix (M) gene are limited. In this study, a large-scale phylogenetic analysis of M gene sequences of avian influenza viruses isolated in China revealed that the M gene has evolved into six different lineages denoted as I-VI. The majority of lineages I and IV were isolated in terrestrial birds, while the majority of lineages II, III, V and VI were isolated in aquatic birds. Lineage I included 148 H9N2 subtype viruses (72.2%), lineage II comprised of 63 H6 subtype viruses (100%), and lineage IV included 157 H5 subtype viruses (97.5%). The mean substitution rates of different lineages ranged from 1.32×10(-3) (lineage III) to 3.64×10(-3) (lineage IV) substitutions per site per year. According to the most recent common ancestor of all lineages, lineage III was the oldest lineage, formed in 1981 or even earlier. And lineage V was the most recent, established around the year 2000. Selective pressure on M2 was stronger than that on M1. The strongest selection pressure was observed in lineage IV. In addition, site-by-site analyses of each lineage identified 8 positive selection sites, all in M2. Most of the sites (5 out of 8) were located in the extracellular domain, which is an antigen for vaccine development. The positive selection sites (amino acid positions 66, 82 and 97) are likely associated with virus budding. This study enhanced our knowledge of M gene evolution of avian influenza viruses, and is expected to improve the early detection of new viruses and lead to vaccine development.
Assuntos
Galinhas/virologia , Vírus da Influenza A/genética , Influenza Aviária/virologia , Doenças das Aves Domésticas/virologia , Sequência de Aminoácidos , Animais , Teorema de Bayes , China , Evolução Molecular , Cadeias de Markov , Filogenia , Seleção Genética , Proteínas da Matriz Viral/genéticaRESUMO
<p><b>OBJECTIVE</b>To investigate the causes of non-hemolytic jaundice among infants in Chongqing, China from the period of 1982 to 2011 and to determine whether the etiologies have changed over the past 30 years.</p><p><b>METHODS</b>The medical records of 3 113 infants,aged 1 month to 1 year,admitted to our hospital with non-hemolytic jaundice were collected and stratified according to decade-long time periods: group A (1982-1991), n=537; group B (1992-2001), n=786; group C (2002-2011), n=1 790. Data on sex, age, etiology and bilirubin level were retrospectively assessed using the chi-square test.</p><p><b>RESULTS</b>In the three groups, boys consistently accounted for the majority of cases (group A:74.3%, group B:66.7%, group C:62.6%). In group A, 52% of the patients were 1-2 months of age; the peak age of patients in both group B and C was 2-3 months (group B:67.8%, group C:61.0%). Group A showed the highest level of patients with mildly elevated total bilirubin level (80.3%); however, moderately elevated total bilirubin level was most frequent in group B (53.4%) and group C (49.7%). The main etiologic diagnoses of the patients in group A were cytomegalovirus (CMV) infection (31.7%), sepsis (18.2%), hepatitis B virus (HBV) (1.3%), and biliary tract anomalies (1.3%); 46.6% of the cases had unclear cause. The main etiologic diagnoses of the cases in group B were CMV infection (36.0%), sepsis (21.5%), breast milk jaundice (2.0%), and HBV (1.9%); 37.9% of the cases had unclear cause. The main etiologic diagnoses of the cases in group C were CMV infection (42.6%), sepsis (7.5%), breast milk jaundice (17.7%), and biliary tract anomalies (2.46%); 29.1% of the cases had unclear cause.</p><p><b>CONCLUSION</b>In Chongqing, infective factors, especially CMV, remain the main cause of nonhemolytic jaundice in infants, but bacterial etiologies have declined over the past 30 years.Non-infective factors, such as biliary tract anomalies and inherited metabolic diseases, have trended upwards. Although there has been great progress in the clinical management of non-hemolytic jaundice in infants, etiological diagnosis remains a challenge and further study is needed to eliminate this condition.</p>