1/290. A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family.Activating mutations of the TSH receptor (TSH-R) have been reported to result in toxic adenomas, multinodular goiters, sporadic neonatal hyperthyroidism, and familial autosomal dominant nonautoimmune hyperthyroidism. To date, all descriptions of such mutations, whether somatic or genomic, have been confined to the Caucasian population. We describe a Chinese family in whom a germline proline to serine substitution in position 639 resulted in familial thyrotoxicosis. This constitutively activating mutation has been previously described in a hyperfunctioning thyroid nodule. The three children in this family developed thyrotoxicosis during childhood; their father was diagnosed as thyrotoxic at the age of 38 yr. Two of the children and the father had mitral valve prolapse (MVP) associated with mitral regurgitation. There was a close temporal relationship between the onset of thyrotoxicosis and the diagnosis of mitral valvular disease in these patients. An increased prevalence of MVP has been reported in Graves' disease and chronic lymphocytic thyroiditis, but the pathophysiological mechanisms linking MVP and autoimmune thyroid disease are still not understood. This is the first report of an association between activating TSH-R mutations and MVP. We postulate that TSH-R activation may increase the clinical expression of MVP in genetically predisposed individuals.- - - - - - - - - - ranking = 1keywords = disease (Clic here for more details about this article) |
2/290. A distinct difference in clinical expression of two siblings with Aicardi-Goutieres syndrome.Two sibs with an encephalopathy, including intracerebral calcification and a white matter disease, are reported. In the younger sister, the cerebrospinal fluid showed chronic pleocytosis and clinically she strictly fits to the diagnosis of Aicardi-Goutieres syndrome. Both sisters were affected by a spastic tetraplegia, truncal hypotonia and dystonic posturing, but the clinical course and the neuroradiological findings were milder in the older sister and she showed no cerebrospinal fluid pleocytosis. The present cases and recent reports of intrafamilial variability of Aicardi-Goutieres syndrome may raise interesting aspects as to the limits and criteria of this syndrome.- - - - - - - - - - ranking = 0.33333333333333keywords = disease (Clic here for more details about this article) |
3/290. Respiratory chain deficiency presenting as recurrent myoglobinuria in childhood.myoglobinuria is an abnormal urinary excretion of myoglobin due to an acute destruction of skeletal muscle fibres. Several metabolic diseases are known to account for myoglobinuria including defects of glycolysis and fatty acid oxidation. Here, we report on respiratory chain enzyme deficiency in three unrelated children with recurrent episodes of myoglobinuria and muscle weakness (complex I: one patient, complex IV: two patients). All three patients had generalized hyporeflexia during attacks, a feature which is not commonly reported in other causes of rhabdomyolysis. Studying respiratory chain enzyme activities in cultured skin fibroblasts might help diagnosing this condition, especially when acute rhabdomyolysis precludes skeletal muscle biopsy during and immediately after episodes of myoglobinuria.- - - - - - - - - - ranking = 0.33333333333333keywords = disease (Clic here for more details about this article) |
4/290. Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis.Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity.- - - - - - - - - - ranking = 0.33333333333333keywords = disease (Clic here for more details about this article) |
5/290. 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 = 0.33333333333333keywords = disease (Clic here for more details about this article) |
6/290. 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 = 1.3333333333333keywords = disease (Clic here for more details about this article) |
7/290. Decision analysis and alzheimer disease: three case studies.Decision analysis may be useful to people facing alzheimer disease (AD) decisions. The use of decision analysis in three such cases is reported. The first case involved a middle-aged person worried about early-onset AD and deciding whether to seek genetic testing. The analysis let the participant reject testing and consider innovative care options. The second case involved a middle-aged person concerned about later-onset AD. The analysis for her was more complex, and led to the assignment of some limited value on genetic testing for her. The third case revolved around a caregiver's treatment decisions for a patient with severe AD. It led her to recognize the importance of factors she had not previously considered. In each of the three cases, the intensive process of decision analysis appears to have improved the subject's decision.- - - - - - - - - - ranking = 1.6666666666667keywords = disease (Clic here for more details about this article) |
8/290. A philosophical critique of decision analysis as a tool in genetic testing.Decision analysis has been proposed as a method to improve the quality of decisions made by individuals facing choices about genetic testing for Alzheimer disease (AD) and other conditions where information about risk is highly uncertain. This paper provides a philosophical critique of two schools of decision analysis, explaining the conceptual limitations inherent in each approach. A central difference between the two approaches is their stance toward the ontological status of patient preferences and values. Are an individual's preferences and values about genetic testing simply assessed or extracted during decision analysis or are they created during the decision analysis itself? How closely can preferences conform to the axioms of rational choice theory? A case study of one individual's experience with decision analysis demonstrates the strengths and weaknesses of decision analysis in the context of genetic testing for AD.- - - - - - - - - - ranking = 0.33333333333333keywords = disease (Clic here for more details about this article) |
9/290. A familial factor in the development of face recognition deficits.The face is probably the single most important visual object. It is the main cue for identifying familiar people and crucial in nonverbal communication. face recognition can be demonstrated in newborn babies, suggesting that face recognition is to some degree 'hard-wired' in the brain. Also, neurological disease can selectively disrupt the ability to recognize faces. Apart from acquired face recognition deficits, developmental cases have been reported. This study presents a family in which the father and two of his daughters are very poor at recognizing faces, demonstrating for the first time a familial factor in developmental face recognition deficit.- - - - - - - - - - ranking = 0.33333333333333keywords = disease (Clic here for more details about this article) |
10/290. coronary artery disease in identical twins.The incidence of coronary artery disease in identical twins is unknown. The knowledge of ischemic heart disease in this patient population is represented by case reports. There is considerable controversy regarding the environmental and genetic factors that play a role in the pathogenesis of this disorder. The natural history of coronary artery disease in an asymptomatic twin with a symptomatic counterpart is unclear. We present a case report and literature review of coronary artery disease in identical twins. On the basis of our patient and the information of other patients, asymptomatic twins of symptomatic counterparts require aggressive assessment and management for occult coronary artery disease.- - - - - - - - - - ranking = 3keywords = disease (Clic here for more details about this article) |
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