Search results for "gene mutation"
showing 10 items of 187 documents
Myocardial 123metaiodobenzylguanidine uptake in genetic Parkinson's disease.
2008
Myocardial (123)Metaiodobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac innervation. MIBG uptake is decreased in nearly all patients with Parkinson's disease (PD). Our objective was to evaluate MIBG uptake in patients with genetic PD. We investigated MIBG uptake in 14 patients with PD associated with mutations in different genes (Parkin, DJ-1, PINK], and leucine-rich repeat kinase 2 -LRRK2), in 15 patients with idiopathic PD, and 10 control subjects. The myocardial MIGB uptake was preserved in 3 of the 4 Parkin-associated Parkinsonisms, in I of the 2 patients with DJ-1 mutations, in 1 of the 2 brothers with PINK] mutations, in 3 of the 6 unrelated patient…
Analysis of thiamine transporter genes in sporadic beriberi
2014
Abstract Objective Thiamine or vitamin B 1 deficiency diminishes thiamine-dependent enzymatic activity, alters mitochondrial function, impairs oxidative metabolism, and causes selective neuronal death. We analyzed for the first time, the role of all known mutations within three specific thiamine carrier genes, SLC19 A2, SLC19 A3 , and SLC25 A19 , in a patient with atrophic beriberi, a multiorgan nutritional disease caused by thiamine deficiency. Methods A 44-year-old male alcoholic patient from Morocco developed massive bilateral leg edema, a subacute sensorimotor neuropathy, and incontinence. Despite normal vitamin B 1 serum levels, his clinical picture was rapidly reverted by high-dose in…
Clinical and genetic characteristics of congenital hypothyroidism due to mutations in the thyroid peroxidase (TPO) gene in Israelis
2007
Summary Objectives Iodide organification defect (IOD) is characterized by a reduced ability of the thyroid gland to retain iodide and results in hypothyroidism. Mutations in the thyroid peroxidase (TPO) gene are a frequent cause of IOD. While TPO mutations have been identified in various populations, none have been reported in Israeli patients with IOD. The objectives of this study were to characterize the molecular basis of IOD in an Israeli Arab-Muslim population and to analyse the clinical, neurological and imaging data of patients with TPO mutations followed for up to 29 years. Patients Twenty-two patients from six core families with congenital hypothyroidism (CH) and IOD living in th…
Primary HBB gene mutation severity and long-term outcomes in a global cohort of β-thalassaemia
2021
In β-thalassaemia, the severity of inherited β-globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long-term outcomes remain limited. We analysed data from 2109 β-thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as β0 /β0 , β0 /β+ , β+ /β+ , β0 /β++ , β+ /β++ , and β++ /β++ . Patients were followed from birth until death or loss to follow-up. The median follow-up time was 34·1 years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, β0 and β+ mu…
Six novel mutations of the LDL receptor gene in FH kindred of Sicilian and Paraguayan descent
2006
Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by mutations in the gene coding for the low density lipoprotein receptor (LDL-R). It is characterized by a high concentration of low density lipoprotein (LDL), which frequently gives rise to premature coronary artery disease. We studied the probands of five FH Sicilian families with 'definite' FH and one proband of Paraguayan descent with homozygous FH who has been treated with an effective living-donor liver transplantation. In order to seek the molecular defect in these six families, we used direct sequencing to define the molecular defects of the LDL-R gene responsible for the disease. We described three…
Refractory Acne and 21-Hydroxylase Deficiency in a Selected Group of Female Patients.
2009
<i>Background:</i> Excessive androgen production, suspected in women when acne is accompanied by hirsutism and menstrual irregularities, may be due to congenital adrenal hyperplasia. This inherited disorder of cortisol biosynthesis is caused in more than 90–95% of all cases by 21-hydroxylase deficiency (21-OHD). The steroid 21-hydroxylase gene <i>(CYP21)</i> has a high degree of variability. <i>Objective:</i> This study was conducted to evaluate <i>CYP21 </i>gene mutations in a selected group of women with papulopustular and comedonal acne refractory to treatment, irregular menses and hirsutism. <i>Methods:</i> 30 out of 61 women e…
Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2…
2009
AbstractData from the Italian Hemophilia Centres were collected to perform a retrospective survey of joint arthroplasty in patients with severe hemophilia. Twenty-nine of 49 hemophilia centers reported that 328 of the 347 operations were carried out in 253 patients with severe hemophilia A (HA) and 19 in 15 patients with severe hemophilia B (HB). When results were normalized to the whole Italian hemophilia population (1770 severe HA and 319 severe HB), patients with HA had a 3-fold higher risk of undergoing joint arthroplasty (odds ratio [OR], 3.38; 95% confidence interval [CI], 1.97-5.77; P < .001). These results were confirmed after adjustment for age, HIV, hepatitis C virus (HCV), and…
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 / …
Genetic polymorphisms affecting the phenotypic expression in familial hypercholesterolemia
2004
The clinical expression of heterozygous familial hypercholesterolemia (FH) is highly variable even in patients carrying the same LDL receptor (LDL-R) gene mutation. This variability might be due to environmental factors as well as to modifying genes affecting lipoprotein metabolism. We investigated Apo E (2, 3, 4), MTP (-493G/T), Apo B (-516C/T), Apo A-V (-1131T/C), HL (-514C/T and -250G/A), FABP-2 (A54T), LPL (D9N, N291S, S447X) and ABCA1 (R219K) polymorphisms in 221 unrelated FH index cases and 349 FH relatives with defined LDL-R gene mutations. We found a significant and independent effect of the following polymorphisms on: (i) plasma LDL-C (Apo E, MTP and Apo B); (ii) plasma HDL-C (HL, …
Azole-resistant Aspergillus fumigatus: A global phenomenon originating in the environment?
2019
Abstract Aspergillus fumigatus is the predominant etiological agent of invasive aspergillosis (IA), a difficult-to-manage fungal disease associated with a high case fatality rate. Azole antifungals, particularly voriconazole, have significantly improved the survival rate of patients with IA. However, the clinical advances made possible through the use of medical azoles could be threatened by the emergence of azole-resistant strains which has been reported in an ever-increasing number of countries over the last 10 years. The major resistance mechanism, that combines point mutation(s) in the coding sequence of cyp51A gene and an insertion of a tandem repeat in the promoter region of this gene…