Search results for " familial"
showing 10 items of 152 documents
Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes.
2018
BACKGROUND: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS: We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution…
Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.
2013
MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration. © 2014 Nature America, Inc. All rights reserved.
CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients
2015
Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n= 64) and apparently sporadic ALS (n= 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHC…
Molecular diagnosis of hypobetalipoproteinemia: an ENID review.
2007
Abstract Primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CRD), with a recessive transmission, and familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission. ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively. Heterozygous FHBL is much more frequent. FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption. FHBL may be linked or not to the APOB gene. Most mutations in APOB gene cause the formation of truncated forms of apoB which may or may be not secreted into the plasma. Truncated apoBs with a size below that of apoB-3…
Benign familial infantile epilepsy associated with KCNQ3 mutation: a rare occurrence or an underestimated event?
2020
Abstract Benign familial infantile epilepsy (BFIE) is the most genetically heterogeneous phenotype among early-onset familial infantile epilepsies. It has an autosomal dominant inheritance pattern with incomplete penetrance. Although PRRT2 is the most mutated gene detected in families with BFIE, other mutations in KCNQ2, SCN2A, and GABRA6 genes have also been described. To date, KCNQ3 mutations have been detected in only four patients with BFIE. Here, we describe the clinical pattern and course of an additional individual with BFIE associated with a novel missense heterozygous KCNQ3 c.1850G>C variant inherited by his unaffected father. The incidence of KCNQ3 mutations among BFIE patients…
Different impacts of cardiovascular risk factors on oxidative stress.
2011
The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant…
A novel mutation in KCNQ3-related benign familial neonatal epilepsy: electroclinical features and neurodevelopmental outcome.
2019
Benign familial neonatal epilepsy (BFNE) is caused, in about 5% of families, by mutations in the KCNQ3 gene encoding voltage-gated potassium channel subunits. Usually, newborns with BFNE show a normal neurological outcome, but recently, refractory seizures and/or developmental disability have been reported suggesting phenotype variability associated with KCNQ3-related BFNE. Here, we describe a proband from a BFNE family carrying a novel variant in the KCNQ3 gene. Regarding the paucity of data in the literature, we describe the presented case with a view to further establishing: (1) a genotype/phenotype correlation in order to define a BFNE phenotype associated with favourable outcome; (2) a…
A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability
2015
Mutations in the KCNQ2 gene encoding for voltage-gated potassium channel subunits have been found in patients affected with early onset epilepsies with wide phenotypic heterogeneity, ranging from benign familial neonatal seizures (BFNS) to epileptic encephalopathy with cognitive impairment, drug resistance, and characteristic electroencephalography (EEG) and neuroradiologic features. By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS. We report clinical, genetic, and functional data from a family in which early onset epilepsy and neurocognitive deficits segregated with a novel mutation in KCNQ3 (c.989G>T; p.R330L). Electrophysiological stu…
Novel mutations of CETP gene in Italian subjects with hyeralphalipoproteinemia
2009
Abstract Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that catalyses the transfer of cholesteryl esters from HDL to the other plasma lipoproteins. Genetic deficiency of CETP is one of the known causes of elevation of plasma HDL-C (primary hyperalphalipoproteinemia, HALP). We sequenced CETP gene in a group of 24 Italian subjects with primary HALP (HDL-C>80 mg/dl) suspected to have CETP deficiency. Two unrelated subjects both coming from the same geographical district, were found to be heterozygous for a nucleotide substitution in exon 6 (c.544C>T) and another subject was found to be heterozygous for a C>T transition in exon 9 (c.802C>T). Both mutations introduce a prema…
Does the longevity of one or both parents influence the health status of their offspring?
2013
According to the findings of some recent studies, the centenarians' offspring appear to represent a promising model for research on longevity and healthy aging. This study compares the health status and the functional status of three groups of subjects: 1. individuals with two long-lived parents (one of whom centenarian), 2. individuals with only one long-lived (centenarian) parent, and 3. individuals with no long-lived parents. The goal is to verify whether the centenarians' offspring display any advantage over the offspring of both non-long-lived parents and to evaluate whether the longevity of the non centenarian parent provides a further advantage. A total of 374 subjects (mean age appr…