1/63. Maternally inherited cardiomyopathy: clinical and molecular characterization of a large kindred harboring the A4300G point mutation in mitochondrial deoxyribonucleic acid.OBJECTIVES: The purpose of this study was to describe the clinical and molecular features of a large family with maternally inherited cardiomyopathy (MICM). BACKGROUND: Recently, several mitochondrial deoxyribonucleic acid (mtDNA) point mutations have been associated with MICM. However, the distinctive clinical and morphologic features of MICM are not fully appreciated. This is partially due to the small size of the reported pedigrees, often lacking detailed clinical and laboratory information. methods: Clinical and genetic analysis of the family was carried out. RESULTS: echocardiography showed mostly symmetrical hypertrophic cardiomyopathy in 10 family members. The illness had an unfavorable course. Progressive heart failure occurred in three subjects, who eventually died; one individual underwent heart transplantation. Electrocardiographic or echocardiographic signs of cardiac hypertrophy in the absence of significant clinical complaints were observed in five subjects. neurologic examination was normal. The mutation was detected in blood from all available subjects. Abundance of mutated molecules ranged between 13% and 100% of total mtDNA genomes. The severity of the disease could not be foreseen by the proportion of mutation in blood. CONCLUSIONS: This report contributes a better description of the clinical aspects of MICM and provides important clues to distinguish it from hypertrophic cardiomyopathy. We suggest that mtDNA mutations, particularly in the transfer ribonucleic acid for isoleucin, should be systematically searched in patients with MICM. The identification of an underlying maternally inherited mitochondrial dna defect in familial cases of cardiomyopathy may considerably influence the management and genetic counseling of affected patients.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
2/63. 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 = 0.0033870925571365keywords = ocular (Clic here for more details about this article) |
3/63. Three hong kong Chinese cases of pretibial epidermolysis bullosa: a genodermatosis that can masquerade as an acquired inflammatory disease.Three patients in two families presented with many years' history of fragile skin, blisters, erosions and scars affecting almost exclusively the shin areas, accompanied by a variable degree of itching. Two of the patients also had toenail dystrophy. skin biopsy revealed dermal-epidermal blister formation and milia but no immunohistochemical evidence of immunoglobulin or complement deposition. Electron microscopic study of the lesional and perilesional skin showed very sparse or absent anchoring fibrils. Immunolabelling for type VII collagen using LH 7.2 monoclonal antibody revealed a bright, linear staining pattern at the dermal-epidermal junction. The clinicopathological features were thus compatible with pretibial epidermolysis bullosa, a subtype of dystrophic epidermolysis bullosa. Of note, the inflammatory nature of the skin lesions, and their resemblance to nodular prurigo and hypertrophic lichen planus, had caused diagnostic difficulties in all cases in the past. A high degree of awareness of this rare subtype of epidermolysis bullosa is important to establish the correct diagnosis, to allow for genetic counselling and to plan clinical management.- - - - - - - - - - ranking = 0.077360243984153keywords = dystrophy (Clic here for more details about this article) |
4/63. Scintigraphic evidence for a specific long-chain fatty acid transporting system deficit and the genetic background in a patient with hypertrophic cardiomyopathy.The mechanism of cardiac uptake of long-chain free fatty acids has not been fully determined. We encountered a hypertrophic cardiomyopathy patient who showed a lack of cardiac uptake of 2 different types of long-chain fatty acid analogues on the scintigraphic images. Flow cytometric analysis revealed no platelet or monocyte CD36 molecule expression (type I CD36 deficiency) and his CD36 gene showed homozygous mutation for 478C to T substitution, leading to an abnormal CD36 amino acid sequence. These findings strongly suggest that a specific transporting system rather than a simple diffusion is commonly involved in the cardiac uptake of long-chain free fatty acids in humans, and that the CD36 protein is the most likely candidate for the specific transporter and to explain scintigraphic defects on fatty acid imaging.- - - - - - - - - - ranking = 0.625keywords = myopathy (Clic here for more details about this article) |
5/63. Recurrent orbital myositis: report of a familial incidence.BACKGROUND: In orbital myositis, painful diplopia develops owing to an enlargement of the extraocular muscles. diagnosis is established based on history, clinical manifestations, and therapeutic response to steroids, with the findings of magnetic resonance imaging providing additional information. observation: We observed a family in which 4 members had an ophthalmopathy suggestive of orbital myositis. The affected members are a sibling pair (female and male) and 2 children of the brothers of their father's father. CONCLUSION: The familial incidence suggests a potential genetic predisposition in the development of orbital myositis.- - - - - - - - - - ranking = 0.0016935462785683keywords = ocular (Clic here for more details about this article) |
6/63. The mitochondrial dna G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS.We report on 4 male patients with clinical, radiological, and muscle biopsy findings typical of the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) phenotype. Skeletal muscle mitochondrial dna (mtDNA) analysis showed that all patients harbored a heteroplasmic G13513A mutation in the ND5 subunit gene. One of these cases (Patient 1) presented with symptoms characteristic of Leber's hereditary optic neuropathy (LHON) 2 years before the first stroke-like episode. Quantitative analysis in several postmortem tissue sections showed that the relative proportions of mutant mtDNA were generally lower than those reported with other pathogenic mtDNA mutations. Single-fiber polymerase chain reaction studies demonstrated significantly higher amounts of mutant mtDNA in ragged red fibers (RRFs) compared with non-RRFs. This study indicates that the G13513A transition is likely to be pathogenic, that it can cause an LHON/MELAS overlap syndrome, and that it may be a more frequent cause of MELAS than previously recognized.- - - - - - - - - - ranking = 0.125keywords = myopathy (Clic here for more details about this article) |
7/63. Merosin-deficient congenital muscular dystrophy and cortical dysplasia.Congenital muscular dystrophy (CMD) encompasses a heterogenous group of muscle disorders with autosomal recessive inheritance, characterized by muscular weakness and hypotonia at birth or within the first few months of life and developmental delay. Merosin-deficient CMD is a clinically distinct form which may be associated with significant abnormalities of the brain detectable by neuroimaging. We report two siblings of consanguineous parents with merosin-deficient CMD in an Irish family who in addition to the characteristic white matter abnormalities on neuroimaging, had occipital dysplasia. Clinical, electrophysiological muscle biopsy findings and neuroimaging were very similar in both cases. Although merosin-deficient CMD with white matter abnormalities on neuroimaging is well documented in the literature, the association with occipital dysplasia has only rarely been reported. The appearance of an identical cortical defect in these siblings suggests an underlying genetic mechanism.- - - - - - - - - - ranking = 7.5636363589863keywords = muscular dystrophy, dystrophy (Clic here for more details about this article) |
8/63. Minicore myopathy in children: a clinical and histopathological study of 19 cases.Minicore myopathy is a congenital myopathy characterized by multifocal areas of degeneration in muscle fibres. genetic heterogeneity expected on the basis of clinical variability awaits further resolution. We reviewed 19 cases in order to further delineate the phenotype. Marked hypotonia was the predominant presenting feature, with evidence of antenatal onset in 30% of cases. Weakness was most pronounced axially and proximally, often more severely affecting the shoulder girdle. Mild facial involvement was frequent. Varying degrees of scoliosis were obvious in all patients older than 10 years. In addition, two patients who were also the most severely affected had complete external ophthalmoplegia. One patient showed marked distal involvement. Respiratory failure developed in half of all patients after 10 years of age and correlated strongly with the degree of scoliosis. Cardiac involvement occurred mainly secondary to respiratory impairment. The course appeared static in most cases. Loss of independent walking was observed only in one case at the age of 10 years. On ultrasound scan, differential involvement within the quadriceps was documented in several patients. Variability in fibre size, type 1 predominance and atrophy with occasional type 2 hypertrophy were prominent but nonspecific histological changes. Apart from typical minicores, a marked increase in internal nuclei was the most prominent histological feature. With the exception of one family in which two generations were affected, inheritance appeared autosomal-recessive or sporadic in all cases.- - - - - - - - - - ranking = 0.76136918122552keywords = myopathy, ophthalmoplegia (Clic here for more details about this article) |
9/63. bartonella henselae associated uveitis and HLA-B27.AIM: To investigate the frequency of HLA-B27 in patients with presumed bartonella henselae associated uveitis and to describe the clinical characteristics of HLA-B27 positive patients with uveitis and presumed ocular bartonellosis (POB). methods: The diagnosis of POB was considered in 19 patients with unexplained uveitis (except for the HLA-B27 association) and high positive IgG (titre >/=1:900) and/or IgM (titre >/=1:250) antibodies against B henselae. In addition to B henselae serology and HLA-B27 typing, all patients underwent an extensive standard diagnostic screening procedure for uveitis and in all cases the results were within the normal limits. The control group consisted of 25 consecutive patients with panuveitis and negative B henselae serology. RESULTS: HLA-B27 was positive in six of the 19 patients (32%) with POB in contrast to the 4% frequency of HLA-B27 in the control group (p=0.03) and 8% prevalence of HLA-B27 in the Dutch population (p=0.003). At the time of positive Bartonella serological testing five of six HLA-B27 positive patients with POB had severe posterior segment involvement with papillitis, macular oedema, and vitreitis. The duration of intraocular inflammatory activity was more than 6 months in five HLA-B27 positive patients. Although four of the six HLA-B27 positive patients had previous recurrent attacks of acute anterior uveitis, the clinical presentation at the time of positive Bartonella serology differed, as illustrated by the involvement of the posterior segment and chronic course of the ocular disease. CONCLUSIONS: The frequency of HLA-B27 in patients with uveitis and serological characteristics of acute infection with B henselae is higher than in the general Dutch population. The findings of this study also suggest a relation between infection with Bartonella species and HLA-B27.- - - - - - - - - - ranking = 0.0050806388357048keywords = ocular (Clic here for more details about this article) |
10/63. myasthenia gravis and associated autoimmune diseases in children.myasthenia gravis has been associated with other autoimmune disorders. We report two children with myasthenia gravis and another autoimmune disease: an 18-month-old boy with ocular myasthenia gravis and Hashimoto's disease and a 14-year-old girl presenting with autoimmune polymyositis, then generalized myasthenia gravis 2 years later. The rare combinations of myasthenia gravis and Hashimoto's disease or polymyositis in children are discussed, and we also briefly review myasthenia gravis and other associated autoimmune diseases in children.- - - - - - - - - - ranking = 0.0016935462785683keywords = ocular (Clic here for more details about this article) |
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