1/14. Clinical phenotype of a Japanese family with primary open angle glaucoma caused by a Pro370Leu mutation in the MYOC/TIGR gene.PURPOSE: To present the phenotype of two patients with primary open angle glaucoma (POAG) caused by a mutation of the myocilin/trabecular meshwork-inducible glucocorticoid response (MYOC/TIGR) gene. methods: Complete ocular examinations were performed on the 13-year-old proband, her father, mother, and sister. dna analysis was performed to detect the mutant gene. RESULTS: The proband and her father were found to have a mutation of the MYOC/TIGR gene. Both patients carried a heterozygous mutation in the 1,109th nucleotide, which corresponds to the 370th amino acid residue of the MYOC/TIGR gene. The clinical characteristics of both patients were: (1) development of POAG at an early age, (2) high peaks of intraocular pressure. and (3) poor response to medical treatment. CONCLUSIONS: The phenotype of these patients with a mutation of the MYOC/TIGR gene agreed with reports of other patients with mutations at other loci in this gene. The discovery of the MYOC/TIGR gene not only makes early detection of glaucoma possible, but also presents a new direction for investigating the pathogenesis of glaucoma.- - - - - - - - - - ranking = 1keywords = pressure (Clic here for more details about this article) |
2/14. Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance.BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. methods: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.- - - - - - - - - - ranking = 1keywords = pressure (Clic here for more details about this article) |
3/14. Uncompacted myelin in hereditary neuropathy with liability to pressure palsies with the 17 p11.2 deletion.A 16-year-old girl with a typical features of hereditary neuropathy with liability to pressure palsies (HNPP) and deletion on chromosome 17p11.2 was described. In the mother who was asymptomatic the same genetic defect was found. In a sural nerve biopsy obtained from the girl myelin thickenings characteristic for this disease and de- and remyelination in nerve fibers were found. Special attention was paid to the occurrence of uncompacted myelin, which was present in diffuse and focal forms. It is concluded that high amount of uncompacted myelin is characteristic for HNPP and it is probably related to the under-expression of peripheral myelin protein 22.- - - - - - - - - - ranking = 5keywords = pressure (Clic here for more details about this article) |
4/14. 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.- - - - - - - - - - ranking = 5keywords = pressure (Clic here for more details about this article) |
5/14. Medulloblastomas in neurofibromatosis type 1. Case report and literature review.A 6-year-old girl, previously diagnosed with neurofibromatosis type 1 (NF-1) presented with ataxia and symptoms of raised intracranial pressure. Diagnostic work up disclosed a posterior fossa tumor. Histopathological study of the excised neoplasm showed a cerebellar medulloblastoma. We review the current literature and suggest that the association of medulloblastoma with NF-1 is not a chance occurrence, and that it might be pathogenically related. We propose that medulloblastoma should be added to the list of malignancies that are apt to occur in NF-1.- - - - - - - - - - ranking = 1keywords = pressure (Clic here for more details about this article) |
6/14. Late-onset apparent mineralocorticoid excess caused by novel compound heterozygous mutations in the HSD11B2 gene.Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, 11beta-HSD2 (HSD11B2), explain the molecular basis for the syndrome of apparent mineralocorticoid excess (AME), characterized by severe hypertension and hypokalemic alkalosis. Cortisol is the offending mineralocorticoid in AME, as the result of a lack of 11beta-HSD2-mediated cortisol to cortisone inactivation. In this study, we describe mutations in the HSD11B2 gene in 3 additional AME kindreds in which probands presented in adult life, with milder phenotypes including the original seminal case reported by Stewart and Edwards. Genetic analysis of the HSD11B2 gene revealed that all probands were compound heterozygotes, for a total of 7 novel coding and noncoding mutations. Of the 7 mutations detected, 6 were investigated for their effects on gene expression and enzyme activity by the use of mutant cDNA and minigene constructs transfected into HEK 293 cells. Four missense mutations resulted in enzymes with varying degrees of activity, all <10% of wild type. A further 2 mutations generated incorrectly spliced mRNA and predicted severely truncated, inactive enzyme. The mothers of 2 probands heterozygous for missense mutations have presented with a phenotype indistinguishable from "essential" hypertension. These genetic and biochemical data emphasize the heterogeneous nature of AME and the effects that heterozygosity at the HSD11B2 locus can have on blood pressure in later life.- - - - - - - - - - ranking = 1keywords = pressure (Clic here for more details about this article) |
7/14. Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation.Primary pulmonary hypertension (PPH) is characterised by sustained elevations of pulmonary arterial pressure without a demonstrable cause, leading to right ventricular failure and death. Hereditary mutations in the bone morphogenetic protein receptor type II (BMPR2) gene result in familial PPH transmitted as an autosomal dominant trait, albeit with low penetrance. The causes in cases without a BMPR2 mutation are unknown, but a syndrome of pulmonary arterial hypertension (PAH) similar to hereditary PPH is associated with systemic connective tissue disease, congenital heart disease, portal hypertension, and human immunodeficiency virus infection, or with the use of appetite-suppressant drugs. The authors identified a BMPR2 gene mutation in a 27-yr-old female who developed PAH after a short course of the appetite-suppressant drug amfepramone (diethylpropion). This allowed molecular genetic counselling and prevention of potentially harmful drug exposure in the patient's son treated for attention deficit disorder with methylphenidate, an amphetamine-related drug. No BMPR2 mutation was found in four additional, unrelated patients with appetite suppressant-related PPH. The findings provide strong evidence that amfepramone can trigger primary pulmonary hypertension in a bone morphogenetic protein receptor type II gene mutation carrier, and indicate that other genes are probably implicated in genetic susceptibility to appetite suppressants.- - - - - - - - - - ranking = 1keywords = pressure (Clic here for more details about this article) |
8/14. Hereditary neuropathy with liability to pressure palsies (HNPP) in a toddler presenting with toe-walking, pain and stiffness.The typical clinical presentation of hereditary neuropathy with liability to pressure palsies is an adult-onset recurrent, painless monoparesis. Electrophysiological abnormalities--decreased nerve conduction velocities and delayed distal latencies--can be detected even in asymptomatic patients. We describe a toddler, who presented with asymmetric toe walking, painful cramps and stiffness in the legs. He had calf hypertrophy, brisk tendon reflexes and bilateral Babinski signs and the electrophysiological examination was normal. The unlikely diagnosis of hereditary neuropathy with liability to pressure palsies was reached 5 years later, when the boy started to complain of episodic numbness and weakness in the upper extremities. His father, paternal aunt and grandmother had similar symptoms, but they had never been investigated. The typical 1.5 Mb deletion on chromosome 17p11.2-12 was found in our patient and his affected relatives.- - - - - - - - - - ranking = 6keywords = pressure (Clic here for more details about this article) |
9/14. Neuropathic scapuloperoneal syndrome (Davidenkow's syndrome) with chromosome 17p11.2 deletion.The nosologic boundary of neuropathic scapuloperoneal syndrome (Davidenkow's syndrome) remains ill defined and its genetic basis is unknown. A case of Davidenkow's syndrome with the monochromosomic 17p11.2 deletion that often is associated with hereditary neuropathy with liability to pressure palsies (HNPP) is described. The other allele at chromosome 17p11.2 locus was of normal length, and direct sequencing of the coding region of the peripheral nerve protein-22 gene in this allele revealed no additional mutation. The deleted allele in the proband was inherited from the paternal line in which the affected members had a late onset Charcot-Marie-tooth type 1 clinical phenotype. This observation suggests that the rare Davidenkow's syndrome is clinically related to HNPP and its genotype could be a chromosome 17p11.2 deletion.- - - - - - - - - - ranking = 1keywords = pressure (Clic here for more details about this article) |
10/14. central nervous system involvement in hereditary neuropathy with liability to pressure palsies: description of a large family with this association.OBJECTIVE: To describe a large family with hereditary neuropathy with liability to pressure palsies associated with central nervous system demyelination. DESIGN: We examined the 18 members of a pedigree. Genetic analysis was performed on 15 subjects, standard nerve conduction studies on 10 subjects, and brain magnetic resonance imaging studies on 8 subjects. RESULTS: Hereditary neuropathy with liability to pressure palsies was confirmed in 9 patients of the pedigree. brain magnetic resonance imaging findings showed multiple areas of demyelination in 6 of 6 affected members and were normal in 2 of 2 healthy relatives. magnetic resonance imaging abnormalities were predominantly located in the subcortical frontal white matter. All patients had acute and recurrent nerve palsies, while clinical features of central nervous system involvement were not a characteristic of this pedigree. CONCLUSIONS: We demonstrate that this association, previously reported in sporadic cases, is not coincidental. Therefore, patients with hereditary neuropathy with liability to pressure palsies can present central nervous system white matter lesions, and the role of the PMP22 (peripheral myelin protein 22) gene deletion in the central nervous system should be further studied.- - - - - - - - - - ranking = 7keywords = pressure (Clic here for more details about this article) |
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