Search results for " Mutation"
showing 10 items of 1212 documents
A Novel Loss of Function Mutation of PCSK9 Gene in White Subjects With Low-Plasma Low-Density Lipoprotein Cholesterol
2007
Objectives— The PCSK9 gene, encoding a pro-protein convertase involved in posttranslational degradation of low-density lipoprotein receptor, has emerged as a key regulator of plasma low-density lipoprotein cholesterol. In African-Americans two nonsense mutations resulting in loss of function of PCSK9 are associated with a 30% to 40% reduction of plasma low-density lipoprotein cholesterol. The aim of this study was to assess whether loss of function mutations of PCSK9 were a cause of familial hypobetalipoproteinemia and a determinant of low-plasma low-density lipoprotein cholesterol in whites. Methods and Results— We sequenced PCSK9 gene in 18 familial hypobetalipoproteinemia subjects and i…
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…
Frequency of NOD2/CARD15 variants in both sporadic and familial cases of Crohn's disease across Italy. An Italian Group for Inflammatory Bowel Diseas…
2004
Abstract Background. Three variants of the NOD 2 /CARD 15 gene are strongly associated with susceptibility to Crohn’s disease; however, striking racial and geographic differences of their frequency have been described. Aims. We have compared the allele frequencies of familial cases of Crohn’s disease recruited in a multicentre study across Italy, in order to disclose possible geographic heterogeneity. Moreover, we also compared the allele frequencies in sporadic cases of Crohn’s disease and healthy controls from Southern Italy with those reported in other two populations from Central and Northern Italy. Subjects and Methods. A total of 731 subjects were genotyped for the polymorphism of thr…
Familial Sotos syndrome caused by a novel missense mutation, C2175S, in NSD1 and associated with normal intelligence, insulin dependent diabetes, bro…
2009
We report a familial Sotos syndrome in two children, boy and girl, aged 17 and 8 years, and in their 44 year old mother, who displayed normal intelligence at adult age, but suffered from insulin dependent diabetes mellitus, bronchial asthma, and severe lipedema. The underlying missense mutation, C2175S, occurred in a conserved segment of the NSD1 gene. Our findings confirm that familial cases of SS are more likely to carry missense mutations. This case report may prove useful to avoid underestimation of the recurrence rate of SS, and to demonstrate that the developmental delay may normalize, enabling an independent life and having an own family.
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…
A Novel APOB Mutation Identified by Exome Sequencing Cosegregates With Steatosis, Liver Cancer, and Hypocholesterolemia
2013
Objective— In familial hypobetalipoproteinemia, fatty liver is a characteristic feature, and there are several reports of associated cirrhosis and hepatocarcinoma. We investigated a large kindred in which low-density lipoprotein cholesterol, fatty liver, and hepatocarcinoma displayed an autosomal dominant pattern of inheritance. Approach and Results— The proband was a 25-year-old female with low plasma cholesterol and hepatic steatosis. Low plasma levels of total cholesterol and fatty liver were observed in 10 more family members; 1 member was affected by liver cirrhosis, and 4 more subjects died of either hepatocarcinoma or carcinoma on cirrhosis. To identify the causal mutation in this f…
Lattice Corneal Dystrophy Type 1
2014
PURPOSE To evaluate the question whether lattice corneal dystrophy type 1 (LCD1) is of epithelial or stromal origin. METHODS The landmark of advanced LCD1 shows central superficial haze and paracentral stromal lattice lines. In 16 eyes of 8 affected individuals of 2 families, a penetrating keratoplasty was performed. The follow-up was 8 to 16 years after penetrating keratoplasty. Slit-lamp documentation of the patients was evaluated in direct and indirect illumination with dilated pupil to assess the horizontal and vertical pattern of new deposits on the corneal graft. Three affected patients of 2 families are demonstrated in detail. A DNA analysis was performed. RESULTS Gene identification…
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…
Detection of a germline mutation and somatic homozygous loss of the von Hippel-Lindau tumor-suppressor gene in a family with a de novo mutation
1996
von Hippel-Lindau (VHL) disease is a pleiotropic disorder featuring a variety of malignant and benign tumors of the eye, central nervous system, kidney, and adrenal gland. Recently the VHL gene has been identified in the chromosomal region 3p25-26. Prognosis and successful management of VHL patients and their descendants depend on unambiguous diagnosis. Due to recurrent hemangioblastomas, a29-year-old patient without familial history of VHL disease was diagnosed to be at risk for the disease. Histopathological examination of a small renal mass identified a clear cell tumor with a G1 grading. Genetic characterization of the germline and of the renal tumor was performed. Polymerase chain reac…