Search results for "mutation."

Tyrosine hydroxylase Val-81-Met polymorphism associated with early-onset alcoholism

2005

The present study examined the association of the Tyrosine hydroxylase Val-81-Met polymorphism with alcohol dependence. One hundred and fifty-nine patients in a psychiatric unit with alcohol dependence were genotyped as well as 92 healthy volunteers. The Val allele was more frequent in patients with alcohol dependence (69.5%) than in controls (62.5%). This effect was largely due to the association with early-onset alcoholism (77.8%), whereas no difference was noted between late-onset patients and controls. Our results suggest a role for tyrosine hydroxylase in early-onset alcoholism.

Enzyme replacement therapy in heterozygous females with Fabry disease: results of a phase IIIB study.

2003

Summary: Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency of α-galactosidase A. Affected patients experience debilitating neuropathic pain and have premature mortality due to renal failure, cardiovascular disease or cerebrovascular complications. The disease may be X-linked dominant, since most females heterozygous for Fabry disease are affected clinically. We evaluated the safety, efficacy and pharmacokinetics of agalsidase alfa (Replagal) administered intravenously to female patients with Fabry disease in an open-label, single-centre study. Fifteen severely affected patients received agalsidase alfa at 0.2 mg/kg every other week for up to 55 weeks. Ag…

Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

2013

Abstract Objective To determine the spectrum of gene mutations and the genotype–phenotype correlations in patients with Autosomal Dominant Hypercholesterolemia (ADH) identified in Italy. Methods The resequencing of LDLR , PCSK9 genes and a selected region of APOB gene were conducted in 1018 index subjects clinically heterozygous ADH and in 52 patients clinically homozygous ADH. The analysis was also extended to 1008 family members of mutation positive subjects. Results Mutations were detected in 832 individuals: 97.4% with LDLR mutations, 2.2% with APOB mutations and 0.36% with PCSK9 mutations. Among the patients with homozygous ADH, 51 were carriers of LDLR mutations and one was an LDLR / …

A further patient with genitopatellar syndrome requiring multidisciplinary management.

2020

Evidence of jak2 val617phe positive essential thrombocythemia with splanchnic thrombosis during estroprogestinic treatment

2008

The discovery of the Janus kinase 2 Val617Phe mutation has brought new insights into the development of myeloproliferative disorders; however, the pathogenesis of essential thrombocythemia and its related thrombotic complications has not been completely understood. Although the Janus kinase 2 Val617Phe mutation confirms the initially suspected clonal character of the disease, factors influencing clonal transformation and expansion in the bone marrow have not been fully detected. Furthermore, patients affected by essential thrombocythemia who are carriers of the Janus kinase 2 Val617Phe mutation show a higher incidence of venous thromboembolism both before, and at the time of diagnosis, comp…

A novel L1CAM mutation in a fetus detected by prenatal diagnosis

2010

X-linked hydrocephalus is due to mutations in the L1 neuronal cell adhesion molecule (L1CAM) gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. We report on a familial case diagnosed by prenatal ultrasonographic examination, with cerebellar hypoplasia, agenesis of the corpus callosum, and the bilateral overlapping of the second and third fingers of the hand. Sequencing of the L1CAM gene showed a novel missense mutation in exon 14: transition of a guanine to cytosine at position 1777 (c.1777G > C), which led to an amino acid change of alanine to proline at position 593 (Ala593Pro) in the sixth immunoglobulin …

Plasma non-cholesterol sterols in primary hypobetalipoproteinemia

2011

Primary hypobetalipoproteinemia (pHBL) is characterized by plasma cholesterol levels ApoB48, and FHBL harbouring as yet unknown molecular defects. Not linked FHBL kindred are not homogeneous in terms of plasma NCS levels. NCS cannot replace genetic HBL analysis.

A 4-year study of the efficacy and tolerability of enzyme replacement therapy with agalsidase alfa in 36 women with Fabry disease

2009

Although Fabry disease is X linked and considered to affect primarily male hemizygotes, female heterozygotes may experience all the signs and symptoms of this metabolic disorder. This prospective, single-center, open-label, clinical trial was performed to evaluate the long-term response of female patients with Fabry disease to enzyme replacement therapy.Symptomatic women (average age = 47 years) enrolled in this 4-year study were treated with agalsidase alfa (Replagal, Shire HGT, Inc.) at a dose of 0.2 mg/kg, every other week for 4 years (N = 36). Clinical and biochemical assessments were conducted at 12-month intervals.The Mainz Severity Score Index, a measure of total disease burden, was …

VITAMIN K-INDUCED MODIFICATION OF COAGULATION PHENOTYPE IN VKORC1 HOMOZYGOUS DEFICIENCY

2008

Summary.  Background: Combined vitamin K-dependent clotting factor (VKCF) deficiency type 2 (VKCFD2) is a rare bleeding disorder caused by mutated vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) gene. Methods and results: An Italian patient with moderate to severe bleeding tendency was genotyped, and found to be homozygous for the unique VKORC1 mutation (Arg98Trp) so far detected in VKCFD2. The activity levels of VKCFs were differentially reduced, and inversely related to the previously estimated affinity of procoagulant factor propeptides for the γ-carboxylase. The normal (factor IX) or reduced antigen levels (other VKCFs) produced a gradient in specific activities. Vitamin K su…

Characterization of epitopes recognized by Candida factor 1 and 9 antisera by use of Saccharomyces cerevisiae mnn mutants

1993

The use of Saccharomyces cerevisiae mnn mutants has facilitated the study of the epitopes recognized by antisera against several antigenic factors of the genus Candida (Candida Check; Iatron Laboratories, Tokyo, Japan). We have taken advantage of the very well characterized structure of the mannans of the different mnn mutants to compare their reactivities with the factor antisera used in the identification of different species of the genus Candida. The results of this study provide evidence that one of the antigenic determinants recognized by factor 1 antisera is the O-linked mannose chains of the cell wall mannoproteins, while that recognized by factor 9 antiserum is the alpha 1-6-linked …