Search results for "mutation."

showing 10 items of 2808 documents

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.

AdultMalemedicine.medical_specialtyPediatricsAdolescentLipid Metabolism DisordersMutation MissenseGermanyInternal medicineImmunopathologyGeneticsHumansMedicineMissense mutationGrowth DisordersGenetics (clinical)AsthmaAutoimmune diseaseType 1 diabetesbusiness.industrySotos syndromeRespiratory diseaseIntracellular Signaling Peptides and ProteinsLipoedemaNuclear ProteinsHistone-Lysine N-MethyltransferaseSyndromeGeneral Medicinemedicine.diseaseAsthmaDiabetes Mellitus Type 1EndocrinologyHistone MethyltransferasesFemalebusinessEuropean Journal of Medical Genetics
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Thrombotic events in systemic lupus erythematosus. Its association with acquired and inherited thrombophilic defects.

2008

Systemic lupus erythematosus (SLE) is characterised by increased venous and arterial thrombotic risk. Although antiphospholipid antibodies (APAs) have been shown to be related with thrombotic tendency in these patients, in more than 40% of them, thrombosis occurs without the presence of such antibodies. We analysed the association of venous and arterial thrombotic events with acquired (anticardiolipin antibodies (ACAs) and lupus anticoagulant (LA)) and inherited (antithrombin (AT), protein C (PC), protein S (PS) deficiencies, factor V Leiden and the prothrombin G20210A mutation), thrombophilic risk factors in 86 SLE patients and 89 healthy controls. Patients showed a higher significant perc…

AdultMalemedicine.medical_specialtyPhysiologyGastroenterologyProtein SRisk FactorsPhysiology (medical)Internal medicinemedicineFactor V LeidenHumansLupus Erythematosus SystemicRisk factorLupus anticoagulantbiologybusiness.industryAntithrombinThrombosisHematologyBlood ProteinsMiddle Agedmedicine.diseaseThrombosisVenous thrombosisAntibodies AnticardiolipinLupus Coagulation InhibitorImmunologyMutationbiology.proteinFemaleCardiology and Cardiovascular MedicinebusinessProtein Cmedicine.drugClinical hemorheology and microcirculation
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Retinal vascular occlusion and deficiencies in the protein C pathway.

1999

Abstract PURPOSE: To report abnormalities in the protein C pathway and other vascular occlusion risk factors in patients with retinal vascular occlusion. METHODS: In a study, we investigated 76 consecutive patients who had in-patient evaluation of venous or arterial retinal vascular occlusion. All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, and resistance to activated protein C and were screened for vascular disease risk factors. Resistance to activated protein C was confirmed by a polymerase chain reaction method to detect the specific factor V R506Q mutation. For comparative purposes, we also scre…

AdultMalemedicine.medical_specialtyRetinal Artery OcclusionDeep veinVascular occlusionGastroenterologyProtein SProtein SCentral retinal vein occlusionRisk FactorsInternal medicineRetinal Vein OcclusionmedicinePrevalenceHumansProspective StudiesActivated Protein C ResistanceAgedRetinal Vascular OcclusionAged 80 and overbiologybusiness.industryFactor VFactor VProtein C DeficiencyMiddle Agedmedicine.diseaseThrombosisSurgeryOphthalmologymedicine.anatomical_structureLupus Coagulation InhibitorMutationbiology.proteinBranch retinal vein occlusionFemalemedicine.symptombusinessProtein CAmerican journal of ophthalmology
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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…

AdultMalemedicine.medical_specialtySLC19 A- SLC25 A19SLC19 AEndocrinology Diabetes and MetabolismGene mutationBeriberimedicine.disease_causeMitochondrial Membrane Transport Proteinslaw.inventionBeriberilawInternal medicineGenotypemedicineThiamine transporterObjective: Thiamine or vitamin B1 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 B1 serum levels his clinical picture was rapidly reverted by high-dose intramuscular thiamine treatment suggesting a possible genetic resistance. We used polymerase chain reaction followed by amplicon sequencing to study all the known thiamine-related gene mutations identified within the Human Gene Mutation Database. Results: Thirty-seven mutations were tested: 29 in SLC19 A2 6 in SLC19 A3 and 2 in SLC25 A19. Mutational analyses showed a wild-type genotype for all sequences investigated. Conclusion: This is the first genetic study in beriberi disease. We did not detect any known mutation in any of the three genes in a sporadic dry beriberi patient. We cannot exclude a role for other known or unknown mutations in the same genes or in other thiamine-associated genes in the occurrence of this nutritional neuropathy.HumansThiamineGenePolymerase chain reactionGeneticsMutationNutrition and DieteticsbiologyMembrane Transport ProteinsThiamine Deficiencymedicine.diseaseAlcoholismEndocrinologyMutationbiology.proteinThiamineMutations
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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…

AdultMalemedicine.medical_specialtySettore MED/09 - Medicina InternaApolipoprotein BNonsense mutationBiologyArticlehypobetaliproteinemia type 1Hypobetalipoproteinemiasexome fatty liver hypobetalipoproteinemia familial 2Young Adultsymbols.namesakeInternal medicinemedicineHumansExomeHEPATOCELLULAR CARCINOMAExomeExome sequencingApolipoproteins Bfatty liverFamily HealthGeneticsSanger sequencingLiver NeoplasmsFatty liverMiddle AgedHEPATOCELLULAR CARCINOMA; exome; fatty liver; hypobetaliproteinemia type 1medicine.diseasePedigreeFatty LiverHypocholesterolemiaCholesterolEndocrinologyCodon Nonsensebiology.proteinsymbolsFemaleCardiology and Cardiovascular MedicineLiver cancerexomeArteriosclerosis, Thrombosis, and Vascular Biology
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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…

AdultMalemedicine.medical_specialtyStromal cellCorneal StromaDNA Mutational AnalysisCorneal graftCorneal KeratocytesCorneal erosionDirect illuminationTransforming Growth Factor betaOphthalmologyTGFBI genemedicineHumansCorneal Dystrophies HereditaryExtracellular Matrix Proteinsbusiness.industryEpithelium Cornealmedicine.diseaseeye diseasesOphthalmologyMutationLattice corneal dystrophyFemalebusinessKeratoplasty PenetratingTGFBICornea
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The clinical use of statistical permutation test methodology: a tool for identifying predictive variables of outcome.

2015

<b><i>Objectives:</i></b> To identify the predictive variables affecting the outcome after radical surgery for bladder cancer by a newer statistical methodology, i.e. nonparametric combination (NPC). <b><i>Methods:</i></b> A multicenter study enrolled 1,312 patients who had undergone radical cystectomy for bladder cancer in 11 Italian oncological centers from January 1982 to December 2002. A statistical analysis<b> </b>of their medical history and diagnostic, pathological and postoperative variables was performed using a NPC test. The<b> </b>patients were included in a comprehensive database with medical history and cli…

AdultMalemedicine.medical_specialtyUrologyStatistics as TopicHydronephrosisnonparametric combinationCystectomyOutcome (game theory)Statistics NonparametricBladder cancer; Permutation test; PrognosisSettore MED/24 - UrologiaBladder cancer Prognosis Permutation testPredictive Value of TestsResamplingMedicineHumansPermutation testRadical surgeryIntensive care medicineAgedNeoplasm StagingRetrospective StudiesAged 80 and overCarcinoma Transitional CellBladder cancerbusiness.industryBladder cancerProstatePermutation testsMiddle Agedmedicine.diseasePrognosisradical surgery for bladder; nonparametric combinationradical surgery for bladderSurgeryPatient Outcome Assessmentbladder cancer; Prognosis; Permutation testsItalyUrinary Bladder NeoplasmsBladdder Cancer Cystectomy outcome statistical methodologyData Interpretation StatisticalLymphatic MetastasisMultivariate AnalysisFemalePredictive variablesradical surgery for bladder nonparametric combinationbusiness
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Intrafamilial variability of the deafness and goiter phenotype in Pendred syndrome caused by a T416P mutation in the SLC26A4 gene.

2004

AbstractPendred syndrome (PS) is the most common cause of syndromic deafness, accounting for more than 5% of all autosomal-recessive hearing loss cases. It is characterized by bilateral sensorineural hearing loss and by goiter with or without hypothyroidism. Mutations in the SLC26A4 gene cause both classical PS and deafness associated with an enlarged vestibular aqueduct without goiter.To investigate a possible genotype-phenotype correlation in PS, we performed a detailed clinical and genetic study in three adult German sibs with typical PS caused by a common homozygous SLC26A4 mutation, T416P. An audiological long-term follow-up of 23 yr showed that the mutation T416P is associated with a …

AdultMalemedicine.medical_specialtyVestibular aqueductGoiterAdolescentHearing lossEndocrinology Diabetes and Metabolismmedicine.medical_treatmentHearing Loss SensorineuralClinical BiochemistryThyroid GlandDeafnessBiochemistryConnexinsEndocrinologyInternal medicineotorhinolaryngologic diseasesmedicineHumansChildPendred syndromebusiness.industryGoiterBiochemistry (medical)ThyroidThyroidectomyMembrane Transport ProteinsSyndromemedicine.diseaseConnexin 26Endocrinologymedicine.anatomical_structurePhenotypeSulfate TransportersChild PreschoolMutationSensorineural hearing lossFemalemedicine.symptombusinessEnlarged vestibular aqueductThe Journal of clinical endocrinology and metabolism
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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…

AdultMalemedicine.medical_specialtyendocrine systemAdolescentEndocrinology Diabetes and MetabolismPopulationDNA Mutational AnalysisConsanguinityGene mutationmedicine.disease_causeIodide PeroxidaseIslamConsanguinityEndocrinologyThyroid peroxidaseInternal medicinemedicineCongenital HypothyroidismHumansGenetic TestingIsraeleducationChildMutationeducation.field_of_studybiologybusiness.industryThyroidPrimary hypothyroidismExonsmedicine.diseaseCongenital hypothyroidismArabsmedicine.anatomical_structureEndocrinologyHaplotypesChild PreschoolMutationbiology.proteinFemalebusinessPolymorphism Restriction Fragment Length
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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…

AdultMalemedicine.medical_specialtyphenotypegenotypemorbidityKaplan-Meier Estimatebeta-GlobinsGene mutationβ thalassaemiaGlobal HealthGastroenterologySeverity of Illness IndexsurvivalCohort StudiesYoung AdultInternal medicineGenotypemedicineLong term outcomesOdds RatioHumansAllelesgenotype; morbidity; mortality; phenotype; survivalProportional Hazards Modelsbusiness.industrybeta-ThalassemiaDisease ManagementHematologyPrognosisPhenotypemortalityConfidence intervalPopulation SurveillanceCohortMutationFemaleRisk of deathbusinessFollow-Up Studies
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