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Asymptomatic Gene Carriers (asymptomatic + gene_carrier)

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Medical Sciences100%

Selected Abstracts

Disease Status in Autosomal Dominant Osteopetrosis Type 2 Is Determined by Osteoclastic Properties,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2006
Kang Chu
Abstract Asymptomatic gene carriers and clinically affected ADO2 subjects have the same ClCN7 mutation. We examined osteoclastic bone resorption in vitro as well as osteoclast formation, several markers, acid secretion, and cytoskeletal structure. We found that ADO2 expression results from osteoclast specific properties. Introduction: Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic disorder that results from heterozygous mutations in the ClCN7 gene. However, of those individuals with a ClCN7 mutation, one third are asymptomatic gene carriers who have no clinical, biochemical, or radiological manifestations. Disease severity in the remaining two thirds is highly variable. Materials and Methods: Human peripheral blood mononuclear cells were isolated and differentiated into osteoclasts by stimulation with hRANKL and human macrophage-colony stimulating factor (hM-CSF). Study subjects were clinically affected subjects, unaffected gene carriers, and normal controls (n = 6 in each group). Pit formation, TRACP staining, RANKL dose response, osteoclast markers, acid secretion, F-actin ring, and integrin ,v,3 expression and co-localization were studied. Results: Osteoclasts from clinically affected subjects had severely attenuated bone resorption compared with those from normal controls. However, osteoclasts from unaffected gene carriers displayed similar bone resorption to those from normal controls. In addition, the resorption lacunae from both unaffected gene carriers and normal controls appeared much earlier and spread much more rapidly than those from clinically affected subjects. As time progressed, the distinction between clinically affected subjects and the other two groups increased. No significant difference was found in acidic secretion or osteoclast formation between the three groups. Osteoclast cytoskeletal organization showed no difference between the three groups but there was low cellular motility in clinically affected subjects. Conclusions: Osteoclasts from the unaffected gene carriers, in contrast to those from the clinically affected subjects, functioned normally in cell culture. This finding supports the hypothesis that intrinsic osteoclast factors determine disease expression in ADO2. Further understanding of this mechanism is likely to lead to the development of new approaches to the treatment of clinically affected patients. [source]

Turcot syndrome confirmed with molecular analysis

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2007
C. Lebrun
Turcot syndrome is clinically characterized by the occurrence of primary brain tumor and colorectal tumor and has, in previous reports, been shown associated with germline mutations in the genes APC, MLH1, MHS6, and PMS2. To date, only few families have been documented by molecular analysis. We report two new families with Turcot syndrome to illustrate and review its characteristics and facilitate diagnosis. Molecular analysis revealed two germline mutations, one in the MLH1 gene and one in MSH2. The latter has never been describe in the literature. Personal and familial relevant anamnestic data from patients with glioma might aid in the diagnosis of genetic disorders. The subsequent molecular characterization may contribute to the appropriate care of affected patients and asymptomatic gene carriers. [source]

Disease Status in Autosomal Dominant Osteopetrosis Type 2 Is Determined by Osteoclastic Properties,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2006
Kang Chu
Abstract Asymptomatic gene carriers and clinically affected ADO2 subjects have the same ClCN7 mutation. We examined osteoclastic bone resorption in vitro as well as osteoclast formation, several markers, acid secretion, and cytoskeletal structure. We found that ADO2 expression results from osteoclast specific properties. Introduction: Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic disorder that results from heterozygous mutations in the ClCN7 gene. However, of those individuals with a ClCN7 mutation, one third are asymptomatic gene carriers who have no clinical, biochemical, or radiological manifestations. Disease severity in the remaining two thirds is highly variable. Materials and Methods: Human peripheral blood mononuclear cells were isolated and differentiated into osteoclasts by stimulation with hRANKL and human macrophage-colony stimulating factor (hM-CSF). Study subjects were clinically affected subjects, unaffected gene carriers, and normal controls (n = 6 in each group). Pit formation, TRACP staining, RANKL dose response, osteoclast markers, acid secretion, F-actin ring, and integrin ,v,3 expression and co-localization were studied. Results: Osteoclasts from clinically affected subjects had severely attenuated bone resorption compared with those from normal controls. However, osteoclasts from unaffected gene carriers displayed similar bone resorption to those from normal controls. In addition, the resorption lacunae from both unaffected gene carriers and normal controls appeared much earlier and spread much more rapidly than those from clinically affected subjects. As time progressed, the distinction between clinically affected subjects and the other two groups increased. No significant difference was found in acidic secretion or osteoclast formation between the three groups. Osteoclast cytoskeletal organization showed no difference between the three groups but there was low cellular motility in clinically affected subjects. Conclusions: Osteoclasts from the unaffected gene carriers, in contrast to those from the clinically affected subjects, functioned normally in cell culture. This finding supports the hypothesis that intrinsic osteoclast factors determine disease expression in ADO2. Further understanding of this mechanism is likely to lead to the development of new approaches to the treatment of clinically affected patients. [source]

Features of the blink reflex in individuals at risk for Huntington's disease

MUSCLE AND NERVE, Issue 11 2001
Marina de Tommaso MD
Abstract The aim of the study was to correlate the features of the blink reflex (BR) with the genetic abnormalities and the clinical findings in patients with Huntington's disease (HD) and asymptomatic gene carriers. Twenty patients with HD and 20 relatives were studied. Mutation analysis was performed for the CAG expansion within the HD gene using HD 333,HD 447 as oligonucleotide primers. The BR was elicited transcutaneously by electrical stimulation of the right supraorbital nerve. The recovery curve of the R2 and R3 responses after a conditioning stimulus was evaluated. R2 latency and duration and R3 duration were significantly increased in HD patients and in presymptomatic carriers in comparison with controls; reduced R2 recovery was also clear in both HD and gene-carrier relatives. In HD patients, the R2 latency increase correlated significantly with the severity of facial chorea. The R2 abnormalities are probably caused by impaired suprasegmental control by the basal ganglia over brainstem interneurons, which may precede the onset of involuntary movements, probably conditioning the severity of facial chorea during development of the disease. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1520,1525, 2001 [source]