HCV viraemia is more important than genotype as a predictor of response to interferon in sicily (Southern Italy)

Abstract Background/Aims: To investigate host- and virus-related factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent. Methods: We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of t…

A genotype-phenotype correlation in Sicilian patients with GJB2 biallelic mutations

The aim of this work was to study the genotype distribution of Sicilian patients with biallelic GJB2 mutations; to correlate genotype classes and/or specific mutations of GJB2 gene (35delG-non-35delG) with audiologic profiles. A total of 10 different mutations and 11 different genotypes were evidenced in 73 SNHL subjects; 35delG (90.36 % of cases) and IVS1+1 (13.69 %) were the most common mutations found in the cohort with a significant difference in the distribution between North and South Sicily. Audiological evaluation revealed a severe (16/73) to profound (47/73) hearing loss (HL) in 86.13 % of cases without significant difference between the degree of HL and the province of origin of t…

Hepatitis C virus replication in ‘autoimmune’ chronic hepatitis

Abstract Both high and low anti-hepatitis C virus antibody (anti-HCV) prevalence has been reported in autoimmune chronic active hepatitis. Therefore, we studied 15 consecutive HBsAg-negative, ELISA anti-HCV-positive, autoantibody-positive patients with biopsy proven chronic active hepatitis in order to confirm ELISA specificity by immunoblot test (RIBA-HCV), and to evaluate HCV replication by serum HCV-RNA. Nine patients were anti-nuclear, three type 1 anti-liver-kidney microsomal and three anti-smooth muscle antibody positive. None had associated autoimmune disease. All cases showed mild clinical disease and only moderate necroinflammatory activity. Response to prednisone was poor. RIBA-HC…

Q289P mutation in the FGFR2 gene: first report in a patient with type 1 Pfeiffer syndrome.

When normal development and growth of the calvarial sutures is disrupted, craniosynostosis (premature calvarial suture fusion) may result. Classical craniosynostosis syndromes are autosomal dominant traits and include Apert, Pfeiffer, Crouzon, Jackson-Weiss, and Saethre-Chotzen syndromes. In these conditions, there is premature fusion of skull bones leading to an abnormal head shape, ocular hypertelorism with proptosis, and midface hypoplasia. It is known that mutations in the fibroblast growth factor receptors 1, 2, and 3 cause craniosynostosis. We report on a child with a clinically diagnosed Pfeiffer syndrome that shows the missense point mutation Q289P in exon 8 of the FGFR2 gene. This …

Glucose 6-phosphate dehydrogenase Palermo R257M: a novel variant associated with chronic non-spherocytic haemolytic anaemia

Genetic and clinical profile of a sicilian population with R92Q mutation

Gene TNFRSF1A mutation is linked to TRAPS, autosomal dominant Autoinflammatory Disease (AID) with recurrent attacks of fever (2-3 weeks long), abdominal pain, vomiting, serositis, arthralgia and/or arthritis, myalgia, fasciitis, rash. The disease starts precociously and amyloidosis is reported in the 25% of the patients. Patients carrying the mutation R92Q usually show a mild clinical phenotype, with an extreme interindividual variability. Arthralgia and serositis are frequently less severe, however oral ulcers and pharyngitis are recurrent. Objectives: We studied the clinical and biochemical impact of the mutation R92Q in our population and the treatment outcome in all the patients with cl…

The role of polymorphisms of thiopurine methyltransferase in therapy with Azathioprine: preliminary study Journal of Biological Research

Azathioprine is an immunosuppressant drug belonging to the class of thiopurines widely used in clinical therapy. Its immunosuppressive action is linked to the substantial action mechanism in the inhibition of the synthesis of nitrogenous bases purine carried out in T-lymphocyte. The level of such medication limit resides in side effects such as myelosuppression and the development of tumours. The occurrence of side effects is linked to the presence of genetic polymorphisms of Thiopurine methyltransferase (TPMT). To date, 40 allelic variants for TPMT have been detected. However, those responsible for the reduction of enzyme activity are three: *2, *3A, *3C. The presence of one of the three p…

Trouble always comes in threes: three mutations for three auto inflammatory genes in a child and in his father

The coexistence of mutations in more than one gene, linked to Autoinflammatory Diesases, can confuse and make difficult the diagnosis and management of these patients, especially in childhood, when the clinical history is still brief.

Identification of D179H, a novel missense GJB2 mutation in a Western Sicily family

The main purpose of this study was to describe a novel missense mutation (p.D179H) found in a Western Sicily family and to examine the genetic and audiologic profiles of all family members by performing a GJB2 and GJB6 mutations analysis and a complete audiologic assessment. The proband was a 3-month-old infant with a congenital profound sensorineural hearing loss; direct sequencing of the GJB2 revealed the presence of a c.35delG mutation in the heterozygous state and a heterozygous G[C transition at nucleotide 535 in trans; this novel mutation, called p.D179H, resulted in an aspartic acid to histidine change at codon 179. It was also evidenced in the heterozygous state in two members of th…

Acalculous cholecystitis during the course of acute Epstein–Barr virus infection and Gilbert's syndrome

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Third-generation hepatitis C virus tests in asymptomatic anti-HCV-positive blood donors

This study evaluated the performance of third-generation anti-HCV assays in blood donors who were positive by second-generation anti-HCV, and assessed any possible relationship between antibody patterns, HCV replication and liver damage. Fifty-two second-generation enzyme immunoassay-positive asymptomatic Italian blood donors were retested for anti-HCV by third-generation enzyme immunoassay and recombinant immunoblot assay (Ortho third-generation enzyme immunoassay, third-generation recombinant immunoblot assay), utilising recombinant C33c and NS5 and synthetic peptide C100 and C22 antigens, and for HCV-RNA by "nested" polymerase chain reaction with 5' region primers. Alanine aminotransfera…

Smouldering hepatitis B virus replication in patients with chronic liver disease and hepatitis delta virus superinfection

Hepatitis B virus deoxyribonucleic acid (HBV-DNA) was studied by Southern blot analysis in liver biopsy specimens from 75 HBsAg-positive patients with chronic liver disease living in southern Italy. Twenty-seven of the patients were hepatitis delta virus (HDV) superinfected. Intrahepatic HBV-DNA was detected in 54 (72%) patients, 32 (59%) of them with replicative forms. The presence of replicative forms was directly related to liver HBcAg and inversely related to liver HDAg, as shown by multivariate analysis. However, 14 patients with intrahepatic HBV-DNA non-replicative pattern and about half of HDV-infected patients were liver HBcAg and/or serum HBV-DNA positive, mostly in low amounts. Hi…

Homozygosity for a Mutation in the CYP11B2 Gene and GH Deficiency in a Child with Severe Growth Delay

Background: Isolated hypoaldosteronism is an autosomal recessive inherited disorder of terminal aldosterone synthesis, leading to selective aldosterone deficiency. Two different biochemical forms of this disease have been described, called aldosterone synthase deficiency or corticosterone methyl oxydase, types 1 and 2. In type 1, there is no aldosterone synthase activity and the 18 hydroxycorticosterone (18 OHB) level is low, whereas in type 2, a residual activity of aldosterone synthase persists and 18 OHB is overproduced. Objective and hypotheses: Isolated aldosterone synthase deficiency should be considered in neonates and infants with failure to thrive and salt wasting. Normal levels of…

Familial mediterranean fever gene (MEVF) mutations in Crohnʼs disease in a Mediterranean area

Long-term course of interferon-treated chronic hepatitis C

Abstract Background/Aims: To evaluate whether sustained response to α-interferon improves clinical outcome in patients with chronic hepatitis C. Methods: A cohort of 410 consecutive patients (65% with chronic hepatitis, 35% with cirrhosis) were treated with α-interferon in two trials (mean follow-up 62.1 months, range 7–109 months). All were serum HCV RNA positive before therapy and received first 10 then 5 million units of α-2b or α-n1 interferon three times weekly for 6 to 12 months. Sustained response was defined as normal aminotransferases 12 months after stopping interferon. Results: Sixty-two patients (15.1%: 54 with chronic hepatitis, eight with cirrhosis) were sustained responders. …

Hepatitis C Viremia in Chronic Liver Disease: Relationship to Interferon-α or Corticosteroid Treatment

We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody–positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p < 0.001). Mean viremia level (× 103 genome equivalents/ml ± S.D.), as assessed with the branched-DNA test, was 5,700 ± 7,618 in the 48 patients wi…

Epidemiological study of nonsyndromic hearing loss in Sicilian newborns

Deafness is caused by a variety of facts, genetic and environmental. Regarding the acquired causes, deafness can be the consequence of prenatal infections, acoustic or cerebral trauma, and the use of ototoxic drugs. Deafness can be the only manifestation (nonsyndromic forms) or it may occur together with other phenotypic findings (syndromic forms). The majority of nonsyndromicdeafness has a genetic basis [Van Camp et al., 1997]. In recent years, deafness and hearing loss have assumed a clinical importance in the study of congenital disorders [Morton et al., 1991]. The clinical interest for hearing loss is supported by the social impact that this disorder has; if not treated, delays in the d…

A randomized controlled trial of high-dose maintenance interferon therapy in chronic hepatitis C

In chronic hepatitis C virus (HCV) infection, the rate of sustained response to interferon is low. We evaluated, in patients responding to a 26-week course of interferon, the effect of high-dose maintenance therapy in preventing relapse. Three hundred and ten patients with chronic HCV infection (38.3% with cirrhosis, 80.6% with HCV type 1) received interferon alfa-2b for 26 weeks (10 MU tiw for 8 weeks, then 5 MU tiw for 18 weeks). One hundred and twenty-four subjects (40%) normalized aminotransferases, and were allocated randomly either to continue on 5 MU tiw for a further 26 weeks (prolonged therapy group: 60 patients) or to stop interferon (brief therapy group: 64 patients). Fifty-two w…

Serum hepatitis C virus (HCV)-RNA and response to alpha-interferon in anti-HCV positive chronic hepatitis

Hepatitis C virus (HCV) replication was assessed before and during alpha-interferon (IFN) treatment in 22 anti-HCV positive patients with posttransfusion or sporadic chronic hepatitis (CH). Eleven patients were “responders” and 11 patients “non-responders” to IFN. Thirteen anti-HCV negative healthy subjects and five anti-HCV negative patients with autoimmune CH served as controls. Serum HCV-RNA was detected by the polymerase chain reaction (PCR) in all untreated anti-HCV positive patients but in none of the anti-HCV negative subjects. PCR primers from the 5′-non-coding (NC) region were more sensitive than primers from a non-structural (NS5) region in detecting HCV-RNA (21/22, 95% vs. 7/22, …

IgM and IgG antibodies to hepatitis C virus in patients with mixed cryoglobulinaemia

SUMMARY To assess the relationship between hepatitis C virus (HCV) infection and essential mixed cryoglobulinaemia (EMC), sera from 23 patients with EMC were tested for IgG and IgM antibodies to HCV antigens and for HCV RNA. Quantitative HCV antibody studies were performed on scrum and purified cryoglobulin fractions. HCV antibodies of both IgG and IgM class were found in 22 (96%) patients. Ten of these were also HCV-RNA positives. Higher litres of anti-HCV IgM were present in the 11 patients with evidence of liver damage. Anti-HCV IgG antibodies were shown to be concentrated in the IgG fraction of cryoglobulins in all eight patients studied. These results strongly suggest a role for HCV in…

A C1-inhibitor rare mutation: Early diagnosis of hereditary angioedema in a paediatric patient

Hereditary angioedema secondary to C1-inhibitor deficiency is a rare autosomal dominant disorder characterized by a deficiency of C1 esterase inhibitor.An eight-year-old girl showed periorbital painless swelling, diagnosed as ethmoiditis. A craniofacial scan did not evidence a paranasal sinus involvement, C1INH levels were undetectable, with low C4 levels: 7.6 mg/dl and C1INH: <8.46 mg/dl. The genetic study identified a rare mutation of the C1INH gene. This clinical report is of relieve because paediatric cases described in literature are rare, did not presented a positive family history, and received a diagnosis after many attacks. Furthermore our girl received a prompt diagnosis of HAE at…

Identification of a new nonsense mutation (Tyr129Stop) of the SRY gene in a newborn infant with XY sex-reversal.

Point mutations and deletions of SRY gene have been described in several cases of XY gonadal dysgenesis. To date, most of these mutations affect the HMG domain of SRY which plays a central role in DNA binding activity of SRY. We report on a non-mosaic XY sex-reversed newborn girl (completely female external genitalia). The direct sequencing of SRY showed a new nonsense mutation in a codon of SRY gene flanking the 3' end of the HMG domain: a thymine is replaced by a guanine at position +387 in codon 129, resulting in the replacement of the amino acid tyrosine (TAT) by a stop codon (TAG). The new mutation of this patient provides further evidence to support the functional importance of the pu…

HCV NS5A mutations in Europeans infected by genotype 1b.

A novel nonsense mutation in exon 2 of the factor IX gene resulting in severe haemophilia B

Clinical and hormonal characteristics in heterozygote carriers of congenital adrenal hyperplasia

Abstract Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing ‘C’ genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carrier…

Genetic and clinical profile of a paediatric population with FMF in Sicily

Familial Mediterranean fever (FMF) is an Autoinflammatory syndrome that is common in children in Mediterranean countries. The real prevalence of FMF in Sicilian children is unknown and need a wide population study. Furthermore, there are no data on the real prevalence of the different mutations between FMF patients and the concordance and/or discordance in clinical and biochemical parameters between patients of different generations.

MTHFR C677T homozygous as risk factor for complications after OLT for cryptogenic cirrhosis

Kawasaki disease triggered by EBV virus in a child with Familial Mediterranean Fever

Abstract Background Familial Mediterranean Fever is a monogenic autoinflammatory disease, secondary to mutation of MEFV gene, and typically expressed with recurrent attacks of fever, serositis, rash, aphthous changes in lips and/or oral mucosa. Kawasaki Disease, an acute systemic vasculitis with persistent fever (5 or more days), rash, stomatitis, conjunctivitis, lymphadenopathy, changes in extremities, is currently considered a multifactorial autoinflammatory disease. An infection, as Epstein Barr virus, can be the trigger of Kawasaki Disease. Case presentation We describe the clinical case of a 3-year-old boy with Kawasaki disease. Successfully treated with intravenous immune globulin, ac…