ABSTRACT
We studied thrombophilic genetic factors (TGFs) MTHFR C677TT, PAI1 4G-4G, V Leiden Q506, prothrombin G20210A as risk factors in 94 patients with HCC with and without portal vein thrombosis (PVT), compared with 214 patients with liver cirrhosis (LC) with and without PVT and 94 healthy controls (HC). The OR (95% CI) for MTHFR C677TT with HCC was 3.85 (1.55-7.39) vs. HC. The OR for PAI1 4G-4G in HCC, was 2.87 (1.27-6.55) vs. HC. Also prothrombin G20210A was significantly more frequent among HCC, mainly in patients with PVT, while V Leiden factor was equally distributed among HCC and HC. Differences were more significant in patients with associated PVT. These findings suggest that frequently TGFs are needed for patients to be at risk of HCC and PVT. We conclude that in all patients with chronic liver disease TGF screening should be performed to individuate patients at risk of HCC and PVT.
Subject(s)
Carcinoma, Hepatocellular/genetics , Factor V/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Plasminogen Activator Inhibitor 1/genetics , Prothrombin/genetics , Thrombosis/genetics , Carcinoma, Hepatocellular/complications , Female , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/genetics , Male , Portal Vein , Thrombosis/complicationsSubject(s)
5,10-Methylenetetrahydrofolate Reductase (FADH2)/genetics , Homozygote , Liver Cirrhosis/genetics , Liver Transplantation/adverse effects , Adult , Biopsy , DNA/genetics , Female , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Male , Middle Aged , Mutation , Postoperative Complications , Risk FactorsABSTRACT
Three patients with different clinical phenotypes harbored the same point mutation at nucleotide 14709 (T14709C) in the tRNAGlu gene of mitochondrial DNA (mtDNA). The first patient was a 21-month-old child with severe congenital myopathy, respiratory distress and mild mental retardation. Muscle biopsy showed about 12% cytochrome c oxidase (COX)-negative ragged-red fibers (RRFs), and markedly decreased activities of mitochondrial respiratory chain complexes I, III and IV. The other two patients were 51- and 55-year-old siblings with slowly progressive myopathy and diabetes mellitus. Muscle biopsy showed focal COX-negative RRFs and decreased activities of complexes I, III and IV. In all three patients, the T14709C mutation was abundant in muscle but present at lower levels in accessible tissues. Previously described patients with the same mutation also showed congenital or late-onset myopathy. Diabetes is frequently associated with both phenotypes and is a clinical clue to the molecular diagnosis.
Subject(s)
DNA, Mitochondrial/genetics , Mitochondrial Myopathies/genetics , Point Mutation , Cysteine/genetics , Cytochrome-c Oxidase Deficiency , DNA Mutational Analysis/methods , Diabetes Complications/complications , Diabetes Complications/genetics , Electron Transport Complex I/metabolism , Electron Transport Complex II/metabolism , Electron Transport Complex III/metabolism , Female , Humans , Infant , Male , Middle Aged , Mitochondrial Myopathies/complications , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , RNA, Transfer/genetics , Threonine/geneticsABSTRACT
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 putative DNA binding activity of the HMG-box domain.
