Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis

Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis.BackgroundFamilial forms of focal segmental glomerulosclerosis (FFSGS) that exhibit autosomal dominant or recessive patterns of inheritance have been described. The genetic basis of these hereditary forms of FSGS is unknown. One recent study of a kindred from Oklahoma with an autosomal dominant form of FSGS linked this disease to a region of chromosome 19q. In addition, polymorphisms in a gene in this region on chromosome 19q13 have been linked to congenital nephrotic syndrome of the Finnish type. We have ascertained and characterized a large family with autosomal dominant FFSGS (Duke 6530).MethodsFamilies were compared for clinical and genetic heterogeneity. To test for linkage of our family to this portion of chromosome 19, genomic DNA was isolated from 102 family members, and polymerase chain reaction was performed using eight microsatellite markers that spanned the area of interest on chromosome 19. Data were evaluated using two-point linkage analysis, multipoint analysis, and an admixture test.ResultsLinkage was excluded at a distance of ±5 to 10cm for all markers tested with two-point log10 of the odds of linkage (LOD) scores and from an approximate 60cm interval in this area of chromosome 19q via multipoint analysis.ConclusionFSGS has been called the “final common pathway” of glomerular injury, as it is a frequent pathological manifestation with diverse etiologies. This diversity likely correlates with the genetic heterogeneity that we have established. Thus, our data demonstrate that there are at least two genes responsible for this disease, and there is genetic as well as clinical heterogeneity in autosomal dominant FSGS

Incidence and severity of cassava mosaic disease in the Republic of Congo

Diagnostic surveys were conducted in 2002 and 2003 in order to provide a comprehensive and detailed assessment of the status of cassava mosaic disease (CMD) in the Republic of Congo (ROC) and to determine if the disease was spreading. In 2002, 105 farmers’ fields were assessed in the four major cassava-producing regions ofthe country. In 2003, 163 fields were sampled in nine regions and Brazzaville Commune. Incidence of cassava mosaic disease was generally high, averaging 80 and 86 % for 2002 and 2003, respectively; while damage was moderate to severe. In 2002, disease incidence was moderate in Pool (73%) but high in Brazzaville (81%),Cuvette Centrale (82%) and in Plateaux Region (84%). Pool region still had the lowest incidence (78%) in 2003, while Sangha (95%) had the highest incidence. The greatest disease severity was recorded in Niari region in the south and Cuvette Ouest region in the north in 2003. East African cassava mosaic virus Uganda variant (EACMVUG) occurred virtually throughout the country, commonly in dual infections with African cassava mosaic virus. The high incidence of disease in plants considered to be the results of cutting infection (74% in 2002 and 82% in 2003), relatively low incidence of disease in plants considered to be infected by whiteflies and wide distribution of EACMV-UG points to the fact that the CMD pandemic is a chronic in the country and the areas sampled are currently in a stable post-epidemic phase. This situation is comparable to that in areas of East Africa affected by a pandemic during the 1990s, including Uganda, parts of western Kenya and north-western Tanzania. These findings clearly verify the assertion that the CMD pendemic has expanded across Central Africa and provide abasis for designing interventions and control strategies for the entire region

Incidence and severity of cassava mosaic disease in the Republic of Congo

Diagnostic surveys were conducted in 2002 and 2003 in order to provide a comprehensive and detailed assessment of the status of cassava mosaic disease (CMD) in the Republic of Congo (ROC) and to determine if the disease was spreading. In 2002, 105 farmers’ fields were assessed in the four major cassava-producing regions of the country. In 2003, 163 fields were sampled in nine regions and Brazzaville Commune. Incidence of cassava mosaic disease was generally high, averaging 80 and 86 % for 2002 and 2003, respectively; while damage was moderate to severe. In 2002, disease incidence was moderate in Pool (73%) but high in Brazzaville (81%), Cuvette Centrale (82%) and in Plateaux Region (84%). Pool region still had the lowest incidence (78%) in 2003, while Sangha (95%) had the highest incidence. The greatest disease severity was recorded in Niari region in the south and Cuvette Ouest region in the north in 2003. East African cassava mosaic virus Uganda variant (EACMVUG) occurred virtually throughout the country, commonly in dual infections with African cassava mosaic virus. The high incidence of disease in plants considered to be the results of cutting infection (74% in 2002 and 82% in 2003), relatively low incidence of disease in plants considered to be infected by whiteflies and wide distribution of EACMV-UG points to the fact that the CMD pandemic is a chronic in the country and the areas sampled are currently in a stable post-epidemic phase. This situation is comparable to that in areas of East Africa affected by a pandemic during the 1990s, including Uganda, parts of western Kenya and north-western Tanzania. These findings clearly verify the assertion that the CMD pendemic has expanded across Central Africa and provide a basis for designing interventions and control strategies for the entire region

Incidence and Severity of Cassava Mosaic Disease in the Republic of Congo

Diagnostic surveys were conducted in 2002 and 2003 in order to provide a comprehensive and detailed assessment of the status of cassava mosaic disease (CMD) in the Republic of Congo (ROC) and to determine if the disease was spreading. In 2002, 105 farmers' fields were assessed in the four major cassava-producing regions of the country. In 2003, 163 fields were sampled in nine regions and Brazzaville Commune. Incidence of cassava mosaic disease was generally high, averaging 80 and 86 % for 2002 and 2003, respectively; while damage was moderate to severe. In 2002, disease incidence was moderate in Pool (73%) but high in Brazzaville (81%), Cuvette Centrale (82%) and in Plateaux Region (84%). Pool region still had the lowest incidence (78%) in 2003, while Sangha (95%) had the highest incidence. The greatest disease severity was recorded in Niari region in the south and Cuvette Ouest region in the north in 2003. East African cassava mosaic virus Uganda variant (EACMV-UG) occurred virtually throughout the country, commonly in dual infections with African cassava mosaic virus. The high incidence of disease in plants considered to be the results of cutting infection (74% in 2002 and 82% in 2003), relatively low incidence of disease in plants considered to be infected by whiteflies and wide distribution of EACMV-UG points to the fact that the CMD pandemic is a chronic in the country and the areas sampled are currently in a stable post-epidemic phase. This situation is comparable to that in areas of East Africa affected by a pandemic during the 1990s, including Uganda, parts of western Kenya and north-western Tanzania. These findings clearly verify the assertion that the CMD pendemic has expanded across Central Africa and provide a basis for designing interventions and control strategies for the entire region.Les enquêtes diagnostiques étaient faites en Janvier 2002 et en Février 2003 en vue d'une évaluation compréhensive et détaillée et mettre à la portée de tous les statuts de la maladie mosaïque du manioc (MMM) en République du Congo (RC) et de déterminer si la maladie pouvait se répandre. Pendant la première année, 105 champs de cultivateurs étaient examinés dans les quatre régions produisant le manioc dans le pays. En 2003, un échantillon de 163 champs étaient sélectionnés dans neuf régions y compris la commune de Brazzaville. L'incidence de la MMM était généralement élevée moyennant respectivement 80 et 86% pour l'année 2002 et 2003, pendant que le dommage s'aggraver de plus en plus. En 2002, l'incidence de la maladie était modérée dans la région du Pool (73%) mais élevée en Brazzaville (81%), dans la cuvette centrale (82%) et la région des plateaux (84%). L'incidence dans la région du Pool demeurait encore plus faible (78%) en 2003 pendant que Sangha avait l'incidence plus élevée (95%). En 2003 la plus grande gravité de la maladie était enregistrée dans la région de Niari au Sud et dans la région Ouest de la cuvette au Nord. La variante du virus de la mosaïque du manioc de l'Afrique de l'Est en Ouganda (VVMMAEO) s'était virtuellement manifestée à travers le pays; les infections s'étaient couplées avec le virus de la mosaïque du manioc africain. La grande incidence de la maladie des plantes considérée être les résultats de la contagion des boutures était de 74% en 2002. Relativement, la basse incidence dans les plantes considérées être contaminées par les mouches blanches et la grande part du VVMMAEO était de 82% en 2003. Ceci a abouti à la conclusion selon laquelle la pandémie de la MMM avait contaminé le pays quelques années auparavant et que les régions ayant fait l'objet de l'échantillon sont actuellement dans une phase post-endémique. Cette situation est comparable à celle des régions de l'Afrique de l'Est qui étaient contaminées par une pandémie les années 1990 y compris l'Ouganda, les parties Ouest du Kenya et le Nord- Ouest de la Tanzanie

Patient beliefs and behaviors about genomic risk for type 2 diabetes: Implications for prevention

Copyright © Taylor & Francis Group, LLC 2015.Type 2 diabetes is a major health burden in the United States, and population trends suggest this burden will increase. High interest in, and increased availability of, testing for genetic risk of type 2 diabetes presents a new opportunity for reducing type 2 diabetes risk for many patients; however, to date, there is little evidence that genetic testing positively affects type 2 diabetes prevention. Genetic information may not fit patients illness representations, which may reduce the chances of risk-reducing behavior changes. The present study aimed to examine illness representations in a clinical sample who are at risk for type 2 diabetes and interested in genetic testing. The authors used the Common Sense Model to analyze survey responses of 409 patients with type 2 diabetes risk factors. Patients were interested in genetic testing for type 2 diabetes risk and believed in its importance. Most patients believed that genetic factors are important to developing type 2 diabetes (67%), that diet and exercise are effective in preventing type 2 diabetes (95%), and that lifestyle changes are more effective than drugs (86%). Belief in genetic causality was not related to poorer self-reported health behaviors. These results suggest that patients interest in genetic testing for type 2 diabetes might produce a teachable moment that clinicians can use to counsel behavior change

Linkage of a Gene Causing Familial Focal Segmental Glomerulosclerosis to Chromosome 11 and Further Evidence of Genetic Heterogeneity

Focal segmental glomerulosclerosis (FSGS) is a pathological entity characterized by proteinuria, nephrotic syndrome, and the progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD). Recently, familial forms of FSGS have been identified. Two families with autosomal dominant FSGS were evaluated for linkage using 351 genomic microsatellite markers. Linkage, multipoint analysis, and tests for heterogeneity were performed on the subsequent results. In addition, three small families were used for haplotype analysis. Evidence for linkage was found on chromosome 11q21–q22 for the largest family, with a maximum lod score of 9.89. The gene is currently localized to an 18-cM area between flanking markers D11S2002 and D11S1986. The disease in a second family was not linked to this locus or to a previously described locus on chromosome 19q13. There were no shared haplotypes among affected individuals in the three smaller families. Our findings demonstrate that genetic heterogeneity is prevalent in FSGS in that at least three genes cause the FSGS phenotype. Identification of the genes that cause familial FSGS will provide valuable insights into the molecular basis and pathophysiology of FSGS

A Duplication in Chromosome 4q35 Is Associated with Hereditary Benign Intraepithelial Dyskeratosis

Hereditary benign intraepithelial dyskeratosis (HBID) is an autosomal dominant disorder characterized by elevated epithelial plaques on the ocular and oral mucous membranes. It has been reported primarily, but not exclusively, in individuals of American Indian heritage in North Carolina. We have examined and obtained DNA on two large families affected by HBID. Using genetic linkage analysis we have localized the HBID gene to chromosome 4 (4q35) with a peak LOD score of 8.97. Molecular analysis of these data reveals that all individuals affected with HBID in both families demonstrate the presence of three alleles for two tightly linked markers, D4S1652 and D4S2390, which map to the telomeric region of 4q35. This suggests the presence of a duplication segregating with the disease phenotype that is most likely involved in its causation