Clinical and genetic variability of oculodentodigital dysplasia.
Explore the source record for details and available documents.
Abnormalities, Multiple↗
Biomedical subjects
F Stögbauer
Publications and source records attributed to F Stögbauer.
Genetic variants of the NOTCH3 gene in migraine--a mutation analysis and association study.
Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Exons 3 and 4 are mutation hotspots. Migraine is a clinical hallmark of CADASIL. The objective of this study was to investigate whether genetic variants in exons 3 and 4 of the NOTCH3 gene are associated with migraine. Exons 3 and 4 of the NOTCH3 were analysed for mutations and polymorphisms by direct DNA sequencing in 97 migraineurs and the same number of control individuals. No mutations in exons 3 and 4 of the NOTCH3 gene were found in 97 patients with migraine. However, association analysis revealed significant association of the single nucleotide polymorphism (SNP) rs1043994 with migraine.
Adolescent↗
Evaluation of single nucleotide polymorphisms in the phosphodiesterase 4D gene (PDE4D) and their association with ischaemic stroke in a large German cohort.
Genetic fine mapping of the first locus identified for genetically complex forms of stroke, STRK1 (which has been mapped to chromosome 5q12 in Icelandic families), has identified the phosphodiesterase 4D gene (PDE4D) gene as a good candidate gene. Association analysis of single nucleotide polymorphisms (SNPs) in the PDE4D gene in an Icelandic stroke cohort demonstrated genetic association between six SNPs in the 5' region of PDE4D and ischaemic stroke. The present study aimed to test whether the same six SNPs in PDE4D were also associated with stroke in a large stroke cohort from northern Germany (stroke patients with acute completed ischaemic stroke: n = 1181; population based controls: n = 1569). None of the six SNPs showed significant association with ischaemic stroke in the whole stroke sample before and after adjustment for conventional stroke risk factors (age, sex, hypertension, diabetes, and hypercholesterolaemia). Haplotype analysis did also not reveal any significant association. Marginally positive statistical measures of association in the subgroup with cardioembolic stroke did not remain significant after correction for multiple testing. In conclusion, this study was unable to demonstrate an association between the six SNPs which had showed significant single marker association with stroke in the Icelandic stroke cohort and ischaemic stroke in a large German cohort.
3',5'-Cyclic-AMP Phosphodiesterases↗
Generalized arteriopathy in patients with cervical artery dissection.
OBJECTIVE: To make an ultrastructural comparison of superficial temporal artery (STA) biopsy specimens from patients with spontaneous cervical artery dissection (sCAD) and controls. METHODS: The authors used light microscopic examination of semithin sections and electron microscopic examination of ultrathin sections of STA biopsy specimens from patients with sCAD and controls. RESULTS: STA biopsy specimens from patients with sCAD taken around the time of the dissection showed a zone of connective tissue weakening with fissuring at the junction between the tunica media (TM) and the tunica adventitia (TA) in seven of nine specimens and erythrocyte infiltration in eight of nine specimens but in none of the control specimens. Light microscopy demonstrated transparent circular spots that, on electron microscopy, turned out to represent erythrocytes and other cellular components at different stages of degradation. Occasionally, scattered immune cells were found in specimens from patients with sCAD. In addition, smooth muscle cells of the synthetic phenotype, some of them showing extensive vacuolation were more common in the TM of STA biopsy specimens from patients with sCAD than in control specimens. CONCLUSIONS: Signs of tissue weakening along the TM/TA junction in STA biopsy specimens of patients with sCAD but not in controls suggest the presence of a generalized arteriopathy leading to impairment of the stability of the arterial wall in patients with sCAD. Limiting factors of the study are that some control biopsies were obtained from autopsies and that the anticoagulation status of patients and controls were not completely comparable.
Adult↗
Electromagnetic fields (GSM 1800) do not alter blood-brain barrier permeability to sucrose in models in vitro with high barrier tightness.
We previously reported that electromagnetic fields (EMFs) [GSM 1800 standard (Global System for Mobile Communications, 1800 MHz)] increased sucrose permeation across the blood-brain barrier (BBB) in vitro. The cell culture model used in our previous study was comprised of rat astrocytes in coculture with porcine brain microvascular endothelial cells (PBECs). In this study, after optimization of cell culture conditions, distinctly improved barrier tightness was observed, accompanied by a loss of susceptibility to EMF-related effects on BBB permeability. Cell cultures were exposed for 1-5 days at an average specific absorption rate (SAR) of 0.3 W/kg in the identical exposure system as described before. To quantify barrier tightness, sucrose permeation across exposed PBEC was measured and compared to values of sham exposed cells and to a control group. Additionally, observations in the BBB coculture system were complemented by similar experiments using two other in vitro models, composed of PBEC monocultures with or without serum. These three models display distinctly higher barrier tightness than the previously used system. In all three BBB models, sucrose permeation across the cell layers remained unaffected by exposure to a GSM 1800 field for up to 5 days. We thus could not confirm enhanced permeability of the BBB in vitro after EMF exposure as reported before since the in vitro barrier tightness in these experiments is now more like that of the in vivo situation.
Animals↗
Protease inhibitors in spontaneous cervical artery dissections.
BACKGROUND AND PURPOSE: Observations in patients with arterial aneurysms, fibromuscular dysplasia, and spontaneous cervical artery dissection (sCAD) indicate that protease inhibitor deficiency might boost the enzymatic destruction of arterial tissue and increase the risk of these arterial wall diseases. Here we present the first large investigation of the protease inhibitor hypothesis in patients with sCAD. METHODS: Eighty patients with sCAD were compared with 80 age- and sex-matched healthy individuals. Alpha1-antitrypsin (alpha1-AT) and alpha2-macroglobulin (alpha2-MG) levels, and alpha1-AT genotypes were assessed and compared between groups. RESULTS: alpha1-AT and alpha2-MG levels as well as alpha1-AT genotypes did not differ significantly between patients and controls. The frequency of Z alleles in the patient group was higher than in the control group and than in other cohorts from Europe; however, the difference remained nonsignificant. All patients with Z alleles had internal carotid artery dissections. CONCLUSIONS: Overall, this data does not support the hypothesis that protease inhibitor levels or alpha1-AT genotypes play an important role in the etiology of sCAD. The present data does not exclude that the Pi-Z allele might have an influence on subgroups of sCAD, such as internal carotid artery dissections.
Adult↗
Autosomal dominant striatal degeneration (ADSD): clinical description and mapping to 5q13-5q14.
OBJECTIVE: To describe the clinical and neuroradiologic features and chromosomal mapping of a novel autosomal dominant disease affecting the basal ganglia. METHODS: The authors characterized a large family with autosomal dominant basal ganglia disease (ADSD) clinically and by MRI, MR spectroscopy (MRS), and SPECT. The authors performed a whole genome genetic linkage scan to map the underlying genetic defect. RESULTS: The main clinical features of the disease are dysarthria and gait disturbance without any apparent reduction in life expectancy. MRI demonstrated a distinctive lesion pattern restricted mainly to the putamen and caudate nucleus. Genetic linkage analysis localized the causative genetic defect to a 3.25 megabase candidate region on chromosome 5q13.3-q14.1. CONCLUSIONS: ADSD is an autosomal dominant basal ganglia disease mapping to chromosome 5q13.3-q14.1.
Basal Ganglia Diseases↗
Cholecystokinin- and cholecystokinin-B-receptor gene polymorphisms in panic disorder.
Panic disorder like other neuropsychiatric disorders is believed to be caused by multiple psychosocial and biological factors. Several lines of evidence point to a role for the peptide neurotransmitter cholecystokinin in the pathogenesis of panic disorder. We therefore determined the allele and genotype frequencies of a single nucleotide polymorphism in the CCK gene (-36C>T) and one CT repeat polymorphism in the CCK-B-receptor gene in a German panic disorder sample (n = 115 for CCK gene polymorphism, n = 111 for CCK-B-receptor polymorphism) and compared them with gender and age matched controls. The length of the polymorphic CT repeat alleles varies between 146 bp and 180 bp. We first analysed the results by a permutation test which provided evidence for heterogeneity between patients and controls (p=0.002). We then analysed the data as a di-allelic polymorphism with a short (146-162bp) and a long (164-180bp) allele and as a tetra-allelic polymorphism with 4 alleles (146-154bp, 156-162bp, 164-170bp, 172-180bp). In the di-allelic analysis as well as in the tetra-allelic analysis there was an excess of the longer allele (p = 0.001) or the two longer alleles (p = 0.041) respectively in patients with panic disorder. No difference between groups was observed for the -36C > T polymorphism. Our findings are consistent with the notion that genetic variation in the CCK neurotransmitter system contributes to the pathogenesis of panic disorder.
Adult↗
[Spontaneous dissection of brain providing neck artery].
Explore the source record for details and available documents.
Aortic Dissection↗
Pneumonia in acute stroke patients fed by nasogastric tube.
BACKGROUND: Aspiration pneumonia is the most important acute complication of stroke related dysphagia. Tube feeding is usually recommended as an effective and safe way to supply nutrition in dysphagic stroke patients. OBJECTIVE: To estimate the frequency of pneumonia in acute stroke patients fed by nasogastric tube, to determine risk factors for this complication, and to examine whether the occurrence of pneumonia is related to outcome. METHODS: Over an 18 month period a prospective study was done on 100 consecutive patients with acute stroke who were given tube feeding because of dysphagia. Intermediate outcomes were pneumonia and artificial ventilation. Functional outcome was assessed at three months. Logistic regression and multivariate regression analyses were used, respectively, to identify variables significantly associated with the occurrence of pneumonia and those related to a poor outcome. RESULTS: Pneumonia was diagnosed in 44% of the tube fed patients. Most patients acquired pneumonia on the second or third day after stroke onset. Patients with pneumonia more often required endotracheal intubation and mechanical ventilation than those without pneumonia. Independent predictors for the occurrence of pneumonia were a decreased level of consciousness and severe facial palsy. The NIH stroke scale score on admission was the only independent predictor of a poor outcome. CONCLUSIONS: Nasogastric tubes offer only limited protection against aspiration pneumonia in patients with dysphagia from acute stroke. Pneumonia occurs mainly in the first days of the illness and patients with decreased consciousness and a severe facial palsy are especially endangered.
Aged↗
Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder.
Panic disorder is an anxiety disorder with an estimated heritability of 48%. Variation in the gene of the nuclear transcription factor "cAMP-responsive element modulator" (CREM) might contribute to its pathogenesis. CREM knock-out mice exhibit significantly less anxiety behavior than wild-type mice and the alternative CREM gene product "inducible cAMP early repressor" (ICER) plays a pivotal role in the hypothalamo-pituitary-adrenal (HPA) axis, which is disturbed in panic disorder. We characterized the genomic organization of the human CREM gene and performed a systematic mutation screening by means of single stranded conformational analysis (SSCA) in a sample of 40 German patients with panic disorder (DSM-III-R). Four novel single nucleotide polymorphisms in CREM promoters P 1 and P 4, one trinucleotide (ATT)-repeat polymorphism in CREM promoter P 2-generating the ICER isoform-and a rare amino acid substitution in CREM exon glut 2 were identified. Association analysis in an extended sample of German patients (n = 88) revealed a significant excess of the shorter CREM P 2 promoter eight-repeat trinucleotide allele and of genotypes containing the eight-repeat trinucleotide allele in panic disorder (P = 0.02), in particular in panic disorder without agoraphobia (P = 0.001). A replication study in independent Italian (n = 76) and Spanish (n = 62) samples, however, failed to confirm this observation. This suggests that the CREM P 2 promoter trinucleotide polymorphism is not a major susceptibility factor in the pathogenesis of panic disorder. Functional analysis of the observed CREM P 2 promoter polymorphism as well as studies in independent panic disorder samples are necessary.
Agoraphobia↗
Spontaneous internal carotid artery dissection and alpha-1-antitrypsin deficiency.
Spontaneous cervical arterial dissection is an important cause of juvenile stroke. However, etiopathology and genetic background remain poorly understood. We report on a 45-year-old-male patient with homozygous alpha-1-antitrypsin (alpha-1-AT) deficiency in whom internal carotid artery dissection occurred in the absence of any other known risk factors. The relevance of alpha-1-AT deficiency for spontaneous cervical arterial dissections is discussed.
Carotid Artery, Internal, Dissection↗
Placing nasogastric tubes in stroke patients with dysphagia: efficiency and tolerability of the reflex placement.
Temporary dysphagia affects up to 50% of stroke patients in the acute stage of their illness and often necessitates tube feeding. In these patients, the placing of nasogastric tubes is often difficult or impossible. This study evaluated the efficiency and tolerability of a previously described new method for tube placing, which utilises the induction of the swallowing reflex and has therefore been called "reflex placement". In 14 of 16 patients in whom the conventional approach failed, the new method was successful. A comparison of the cardiovascular responses to both methods in another 12 patients revealed significantly smaller increases in heart rate and systolic blood pressure during application of the new method. We therefore suggest the use of reflex placement in patients who have suffered a stroke and need tube feeding due to dysphagia.
Aged↗
Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene.
Giant axonal neuropathy (GAN) is an autosomal recessive neurologic disorder clinically characterized by a severe polyneuropathy, CNS abnormalities, and characteristic tightly curled hair. Recently, mutations in the gigaxonin gene have been identified as the underlying genetic defect. The authors report two novel mutations confirming that GAN is caused by mutations in the gigaxonin gene and raise the question whether some mutations may cause a mild subclinical neuropathy.
Adolescent↗
Simple method for placing nasogastric tubes in patients with dysphagia.
Patients who have had an acute stroke often have dysphagia and tube feeding becomes necessary. In these patients placing nasogastric tubes is often difficult, or even impossible. We describe a simple method for placing nasogastric tubes by inducing the swallowing reflex, which is independent of the patient's ability to co-operate. Among nine patients for whom the conventional methods had failed 20 placements were made, 19 of which were successful. Our approach is much less distressing for patients than conventional methods.
Aged↗
Brachial plexus involvement as the only expression of hereditary neuropathy with liability to pressure palsies.
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant focal neuropathy characterized by recurrent entrapment neuropathies. Single members of families with HNPP and brachial plexus involvement have been reported previously. We describe a family with three affected members and in which the only symptom of entrapment was recurrent brachial plexopathy. The diagnosis of HNPP in this family was confirmed by both neurophysiological methods and DNA analysis. The distinction between HNPP and hereditary neuralgic amyotrophy is discussed.
Adult↗
Hereditary Neuralgic Amyotrophy (HNA) is genetically heterogeneous.
Hereditary Neuralgic Amyotrophy (HNA) is an autosomal dominantly inherited recurrent focal neuropathy affecting mainly the brachial plexus. Linkage to markers on chromosome 17q25 was found in 1996 and subsequent reports confirmed linkage of HNA to this locus. Recently a family with a chronic undulating rather than remitting-relapsing clinical course of HNA was described by a Dutch group. This family did not have linkage to the 17q25 locus. Here we describe for the first time clinically and genetically two families with classic remitting-relapsing HNA that are not linked to the previously described HNA locus on chromosome 17q25. These results demonstrate that clinically homogeneous classical HNA is genetically heterogeneous.
Adult↗
Mutation analysis in Chariot-Marie Tooth disease type 1: point mutations in the MPZ gene and the GJB1 gene cause comparable phenotypic heterogeneity.
Charcot-Marie-Tooth disease type 1 (CMT1) is a demyelinating peripheral neuropathy most commonly caused by a DNA duplication on chromosome 17p11.2 including the peripheral myelin protein 22 (PMP22). Point mutations in the myelin protein zero gene (MPZ) and gap junction protein, beta-1 gene (GJB1) are also found in association with CMT1 or the subclass of CMT type X (CMTX), respectively. Recently point mutations in these genes have been found in patients showing the axonal variant of CMT, CMT type 2 (CMT2). We here describe the clinical and electro-physiological findings caused by two novel and two recently described MPZ mutations and six GJB1 mutations. Different MPZ and GJB1 mutations were associated with different grades of severity in CMT1 and CMTX. The novel MPZ Glu141st op mutation was associated with the axonal CMT2. We conclude that the clinical and electrophysiological heterogeneity among CMT patients carrying point mutations in MPZ and GJB1 is similar. Thus for clinical purposes CMT1 and CMT2 patients should be screened for mutations in these two genes after duplication on chromosome 17p11.2 has been excluded as the disease causing mutation.
Adolescent↗