Search results for "Heterozygosity"
showing 10 items of 150 documents
TBC1D24-TLDc-related epilepsy exercise-induced dystonia: rescue by antioxidants in a disease model
2019
Genetic mutations in TBC1D24 have been associated with multiple phenotypes, with epilepsy being the main clinical manifestation. The TBC1D24 protein consists of the unique association of a Tre2/Bub2/Cdc16 (TBC) domain and a TBC/lysin motif domain/catalytic (TLDc) domain. More than 50 missense and loss-of-function mutations have been described and are spread over the entire protein. Through whole genome/exome sequencing we identified compound heterozygous mutations, R360H and G501R, within the TLDc domain, in an index family with a Rolandic epilepsy exercise-induced dystonia phenotype (http://omim.org/entry/608105). A 20-year long clinical follow-up revealed that epilepsy was self-limited in…
Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations: molecular and in silico studies.
2007
CONTEXT AND OBJECTIVE: Most cases of goitrous congenital hypothyroidism (CH) from thyroid dyshormonogenesis 1) follow a recessive mode of inheritance and 2) are due to mutations in the thyroid peroxidase gene (TPO). We report the genetic mechanism underlying the apparently dominant inheritance of goitrous CH in a nonconsanguineous family of French Canadian origin. DESIGN, SETTING, AND PARTICIPANTS: Two brothers identified by newborn TSH screening had severe hypothyroidism and a goiter with increased (99m)Tc uptake. The mother was euthyroid, but the father and two paternal uncles had also been diagnosed with goitrous CH. After having excluded PAX8 gene mutations, we hypothesized that the und…
Infant developmental profile of Crisponi syndrome due to compound heterozygosity for CRLF1 deletion.
2020
Crisponi syndrome/CISS1, is an autosomal recessive ciliary neurotrophic factor receptor (CNTFR)-related genodermatosis caused in 95% of cases by mutations in CRLF1 on chromosome 19p13. The CNTFR pathway is important for CNS development. Crisponi syndrome/ CISS1 can be suspected in the presence of the following clinical triad: camptodactyly with fisted hands, intermittent hyperthermia and muscular contractions with feeding difficulties.
Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia.
2012
Objective— Mutations of the ANGPTL3 gene have been associated with a novel form of primary hypobetalipoproteinemia, the combined hypolipidemia (cHLP), characterized by low total cholesterol and low HDL-cholesterol levels. The aim of this work is to define the role of ANGPTL3 gene as determinant of the combined hypolipidemia phenotype in 2 large cohorts of 913 among American and Italian subjects with primary hypobetalipoproteinemia (total cholesterol <5th percentile). Methods and Results— The combined hypolipidemia cut-offs were chosen according to total cholesterol and HDL-cholesterol levels reported in the ANGPTL3 kindred described to date: total cholesterol levels, <2nd percentile …
Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia.
2015
Background: Monogenic hypertriglyceridemia (HTG) may result from mutations in some genes which impair the intravascular lipolysis of triglyceride (TG)-rich lipoproteins mediated by the enzyme Lipoprotein lipase (LPL). Mutations in the LPL gene are the most frequent cause of monogenic HTG (familial chylomicronemia) with recessive transmission. Methods: The LPL gene was resequenced in 149 patients with severe HTG (TG>10mmol/L) and 106 patients with moderate HTG (TG>4.5 and <10mmol/L) referred to tertiary Lipid Clinics in Italy. Results: In the group of severe HTG, 26 patients (17.4%) were homozygotes, 9 patients (6%) were compound heterozygotes and 15 patients (10%) were simple heter…
Mutations in the PDS Gene in German Families with Pendred’s Syndrome: V138F Is a Founder Mutation
2003
Pendred's syndrome, an autosomal-recessive condition characterized by congenital sensorineural hearing loss and goiter, is caused by mutations in the PDS gene. Located on chromosome 7q22-q31, it encodes a chloride-iodide transporter expressed in the thyroid, inner ear, and kidney. We investigated the PDS gene of six affected individuals from four unrelated families with Pendred's syndrome by direct sequencing. PDS mutations were identified in homozygous or compound heterozygous state in all six cases. A homozygous missense mutation leading to the amino acid substitution S133T was detected in a family of Turkish origin. The mutations found in the other affected individuals, who originate fro…
Mutations in SLC13A5 Cause Autosomal-Recessive Epileptic Encephalopathy with Seizure Onset in the First Days of Life
2014
International audience; Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due …
A novel mutation of the DHCR7 gene in a sicilian compound heterozygote with Smith-Lemli-Opitz Syndrome
2005
Introduction: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis, resulting from deficient 7-dehydrocholesterol reductase (3β-hydroxysterol Δ7-reductase) activity, the enzyme responsible for conversion of 7-dehydrocholesterol to cholesterol. SLOS is most common among people of European descent, with a reported incidence of 1 per 20 000–60 000 newborns, depending on the diagnostic criteria and the reference population. More than 80 different mutations have been identified in several hundred patients. In Italy, SLOS appears to be a rare condition, probably because of underdiagnosis. Method: We analyzed by direct sequencing the 7-dehydrocholesterol…
Two novel mutations in the human thyroid peroxidase (TPO) gene: genetics and clinical findings in four children
2009
UNLABELLED We report four children originating from two unrelated German families with congenital hypothyroidism (CH) due to mutations in the thyroid peroxidase (TPO) gene. Three female siblings (family 1) were found to be compound heterozygous for two mutations, a known mutation in exon 9 (W527C), and a mutation in exon 8 (Q446H), which has not been described before. In the second family we identified a boy with goitrous CH, who had a novel homozygous mutation in the TPO gene in exon 16 (W873X). All children of family 1 were diagnosed postnatally by newborn screening. The case of the boy of family 2 has already been reported for the in utero treatment of a goiter with hypothyroidism. CONCL…
Mutations in the HFE gene and cardiovascular disease risk: an individual patient data meta-analysis of 53 880 subjects.
2008
Background— Whether mutations in the hemochromatosis (HFE) gene increase cardiovascular disease risk is still undetermined. The main reason is the low frequency of the mutations, in particular of the compound C282Y/H63D genotype. We combined the data of 11 observational studies for an individual patient data meta-analysis. Methods and Results— Individual patient data were obtained from published as well as unpublished studies that had information available on the C282Y mutation as well as the H63D mutation in relation to coronary heart disease risk. Individual records were provided on each of the 53 880 participants in 11 studies. In total, 10 541 patients with coronary events were documen…