The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Konstantin Petrukhin - One of the best experts on this subject based on the ideXlab platform.
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The mutation spectrum of the bestrophin protein--functional implications.
Human genetics, 1999Co-Authors: B. Bakall, Ola Sandgren, Towa Marknell, Sofie Ingvast, Markus J. Koisti, Arthur A. B. Bergen, Sten Andreasson, Tomas Rosenberg, Konstantin PetrukhinAbstract:Best’s Macular dystrophy (BMD), also known as Vitelliform Macular Degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of Macular Degeneration with mainly juvenile onset. BMD is characterized by the accumulation of lipofuscin within and beneath the retinal pigment epithelium. The gene causing the disease has been localized to 11q13 by recombination breakpoint mapping. Recently, we have identified the causative gene encoding a protein named bestrophin, and mutations have been found mainly to affect residues that are conserved from a family of genes in Caenorhabditis elegans. The function of bestrophin is so far unknown, and no reliable predictions can be made from sequence comparisons. We have investigated the bestrophin gene in 14 unrelated Swedish, Dutch, Danish, and Moroccan families affected with BMD and found eight new mutations. Including the previously published mutations, 15 different missense mutations have now been detected in 19 of the 22 families with BMD investigated by our laboratory. Interestingly, the mutations cluster in certain regions, and no nonsense mutations or mutations causing frame-shifts have been identified. Computer simulations of the structural elements in the bestrophin protein show that this protein is probably membrane bound, with four putative transmembrane regions.
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The mutation spectrum of the bestrophin protein – functional implications
Human Genetics, 1999Co-Authors: B. Bakall, Ola Sandgren, Towa Marknell, Sofie Ingvast, Markus J. Koisti, Arthur A. B. Bergen, Sten Andreasson, Tomas Rosenberg, Konstantin Petrukhin, Claes WadeliusAbstract:Best’s Macular dystrophy (BMD), also known as Vitelliform Macular Degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of Macular Degeneration with mainly juvenile onset. BMD is characterized by the accumulation of lipofuscin within and beneath the retinal pigment epithelium. The gene causing the disease has been localized to 11q13 by recombination breakpoint mapping. Recently, we have identified the causative gene encoding a protein named bestrophin, and mutations have been found mainly to affect residues that are conserved from a family of genes in Caenorhabditis elegans . The function of bestrophin is so far unknown, and no reliable predictions can be made from sequence comparisons. We have investigated the bestrophin gene in 14 unrelated Swedish, Dutch, Danish, and Moroccan families affected with BMD and found eight new mutations. Including the previously published mutations, 15 different missense mutations have now been detected in 19 of the 22 families with BMD investigated by our laboratory. Interestingly, the mutations cluster in certain regions, and no nonsense mutations or mutations causing frame-shifts have been identified. Computer simulations of the structural elements in the bestrophin protein show that this protein is probably membrane bound, with four putative transmembrane regions.
Claes Wadelius - One of the best experts on this subject based on the ideXlab platform.
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The mutation spectrum of the bestrophin protein – functional implications
Human Genetics, 1999Co-Authors: B. Bakall, Ola Sandgren, Towa Marknell, Sofie Ingvast, Markus J. Koisti, Arthur A. B. Bergen, Sten Andreasson, Tomas Rosenberg, Konstantin Petrukhin, Claes WadeliusAbstract:Best’s Macular dystrophy (BMD), also known as Vitelliform Macular Degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of Macular Degeneration with mainly juvenile onset. BMD is characterized by the accumulation of lipofuscin within and beneath the retinal pigment epithelium. The gene causing the disease has been localized to 11q13 by recombination breakpoint mapping. Recently, we have identified the causative gene encoding a protein named bestrophin, and mutations have been found mainly to affect residues that are conserved from a family of genes in Caenorhabditis elegans . The function of bestrophin is so far unknown, and no reliable predictions can be made from sequence comparisons. We have investigated the bestrophin gene in 14 unrelated Swedish, Dutch, Danish, and Moroccan families affected with BMD and found eight new mutations. Including the previously published mutations, 15 different missense mutations have now been detected in 19 of the 22 families with BMD investigated by our laboratory. Interestingly, the mutations cluster in certain regions, and no nonsense mutations or mutations causing frame-shifts have been identified. Computer simulations of the structural elements in the bestrophin protein show that this protein is probably membrane bound, with four putative transmembrane regions.
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Refined genetic localization of the Best disease gene in 11q13 and physical mapping of linked markers on radiation hybrids
Human Genetics, 1997Co-Authors: Caroline Graff, Anna Eriksson, Kristina Forsman, Ola Sandgren, Gösta Holmgren, Claes WadeliusAbstract:Best’s Macular dystrophy, also known as Vitelliform Macular Degeneration type 2 (VMD-2), is an autosomal dominant eye disorder that causes reduced visual acuity. It generally manifests itself in the teenage years. The gene mutated in VMD-2 patients may provide valuable insight into the biological mechanisms of the far more common disorder age-related Macular Degeneration. The VMD-2 gene has been localized to 11q13 between UGB and FcɛRI. In order to clone the gene positionally, a large Swedish VMD-2 family dating back to the 17th century was studied for recombinations. Since the last study, another 40 microsatellite markers have been analyzed in the family; the closest centromeric flanking marker, D11S4076, revealed two recombinations and the closest telomeric flanking marker, UGB, revealed one recombination. The recombinations have occurred in affected individuals, which eliminates the potential problem of reduced penetrance. The order and physical distance between 22 markers located at proximal 11q13 were analyzed on the G3 Stanford radiation-reduced cell hybrids. The data suggest that the VMD-2 region flanked by the microsatellite markers D11S4076 and UGB is approximately 980 kb.
B. Bakall - One of the best experts on this subject based on the ideXlab platform.
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The mutation spectrum of the bestrophin protein--functional implications.
Human genetics, 1999Co-Authors: B. Bakall, Ola Sandgren, Towa Marknell, Sofie Ingvast, Markus J. Koisti, Arthur A. B. Bergen, Sten Andreasson, Tomas Rosenberg, Konstantin PetrukhinAbstract:Best’s Macular dystrophy (BMD), also known as Vitelliform Macular Degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of Macular Degeneration with mainly juvenile onset. BMD is characterized by the accumulation of lipofuscin within and beneath the retinal pigment epithelium. The gene causing the disease has been localized to 11q13 by recombination breakpoint mapping. Recently, we have identified the causative gene encoding a protein named bestrophin, and mutations have been found mainly to affect residues that are conserved from a family of genes in Caenorhabditis elegans. The function of bestrophin is so far unknown, and no reliable predictions can be made from sequence comparisons. We have investigated the bestrophin gene in 14 unrelated Swedish, Dutch, Danish, and Moroccan families affected with BMD and found eight new mutations. Including the previously published mutations, 15 different missense mutations have now been detected in 19 of the 22 families with BMD investigated by our laboratory. Interestingly, the mutations cluster in certain regions, and no nonsense mutations or mutations causing frame-shifts have been identified. Computer simulations of the structural elements in the bestrophin protein show that this protein is probably membrane bound, with four putative transmembrane regions.
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The mutation spectrum of the bestrophin protein – functional implications
Human Genetics, 1999Co-Authors: B. Bakall, Ola Sandgren, Towa Marknell, Sofie Ingvast, Markus J. Koisti, Arthur A. B. Bergen, Sten Andreasson, Tomas Rosenberg, Konstantin Petrukhin, Claes WadeliusAbstract:Best’s Macular dystrophy (BMD), also known as Vitelliform Macular Degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of Macular Degeneration with mainly juvenile onset. BMD is characterized by the accumulation of lipofuscin within and beneath the retinal pigment epithelium. The gene causing the disease has been localized to 11q13 by recombination breakpoint mapping. Recently, we have identified the causative gene encoding a protein named bestrophin, and mutations have been found mainly to affect residues that are conserved from a family of genes in Caenorhabditis elegans . The function of bestrophin is so far unknown, and no reliable predictions can be made from sequence comparisons. We have investigated the bestrophin gene in 14 unrelated Swedish, Dutch, Danish, and Moroccan families affected with BMD and found eight new mutations. Including the previously published mutations, 15 different missense mutations have now been detected in 19 of the 22 families with BMD investigated by our laboratory. Interestingly, the mutations cluster in certain regions, and no nonsense mutations or mutations causing frame-shifts have been identified. Computer simulations of the structural elements in the bestrophin protein show that this protein is probably membrane bound, with four putative transmembrane regions.
Ola Sandgren - One of the best experts on this subject based on the ideXlab platform.
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The mutation spectrum of the bestrophin protein--functional implications.
Human genetics, 1999Co-Authors: B. Bakall, Ola Sandgren, Towa Marknell, Sofie Ingvast, Markus J. Koisti, Arthur A. B. Bergen, Sten Andreasson, Tomas Rosenberg, Konstantin PetrukhinAbstract:Best’s Macular dystrophy (BMD), also known as Vitelliform Macular Degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of Macular Degeneration with mainly juvenile onset. BMD is characterized by the accumulation of lipofuscin within and beneath the retinal pigment epithelium. The gene causing the disease has been localized to 11q13 by recombination breakpoint mapping. Recently, we have identified the causative gene encoding a protein named bestrophin, and mutations have been found mainly to affect residues that are conserved from a family of genes in Caenorhabditis elegans. The function of bestrophin is so far unknown, and no reliable predictions can be made from sequence comparisons. We have investigated the bestrophin gene in 14 unrelated Swedish, Dutch, Danish, and Moroccan families affected with BMD and found eight new mutations. Including the previously published mutations, 15 different missense mutations have now been detected in 19 of the 22 families with BMD investigated by our laboratory. Interestingly, the mutations cluster in certain regions, and no nonsense mutations or mutations causing frame-shifts have been identified. Computer simulations of the structural elements in the bestrophin protein show that this protein is probably membrane bound, with four putative transmembrane regions.
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The mutation spectrum of the bestrophin protein – functional implications
Human Genetics, 1999Co-Authors: B. Bakall, Ola Sandgren, Towa Marknell, Sofie Ingvast, Markus J. Koisti, Arthur A. B. Bergen, Sten Andreasson, Tomas Rosenberg, Konstantin Petrukhin, Claes WadeliusAbstract:Best’s Macular dystrophy (BMD), also known as Vitelliform Macular Degeneration type 2 (VMD2; OMIM 153700), is an autosomal dominant form of Macular Degeneration with mainly juvenile onset. BMD is characterized by the accumulation of lipofuscin within and beneath the retinal pigment epithelium. The gene causing the disease has been localized to 11q13 by recombination breakpoint mapping. Recently, we have identified the causative gene encoding a protein named bestrophin, and mutations have been found mainly to affect residues that are conserved from a family of genes in Caenorhabditis elegans . The function of bestrophin is so far unknown, and no reliable predictions can be made from sequence comparisons. We have investigated the bestrophin gene in 14 unrelated Swedish, Dutch, Danish, and Moroccan families affected with BMD and found eight new mutations. Including the previously published mutations, 15 different missense mutations have now been detected in 19 of the 22 families with BMD investigated by our laboratory. Interestingly, the mutations cluster in certain regions, and no nonsense mutations or mutations causing frame-shifts have been identified. Computer simulations of the structural elements in the bestrophin protein show that this protein is probably membrane bound, with four putative transmembrane regions.
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Refined genetic localization of the Best disease gene in 11q13 and physical mapping of linked markers on radiation hybrids
Human Genetics, 1997Co-Authors: Caroline Graff, Anna Eriksson, Kristina Forsman, Ola Sandgren, Gösta Holmgren, Claes WadeliusAbstract:Best’s Macular dystrophy, also known as Vitelliform Macular Degeneration type 2 (VMD-2), is an autosomal dominant eye disorder that causes reduced visual acuity. It generally manifests itself in the teenage years. The gene mutated in VMD-2 patients may provide valuable insight into the biological mechanisms of the far more common disorder age-related Macular Degeneration. The VMD-2 gene has been localized to 11q13 between UGB and FcɛRI. In order to clone the gene positionally, a large Swedish VMD-2 family dating back to the 17th century was studied for recombinations. Since the last study, another 40 microsatellite markers have been analyzed in the family; the closest centromeric flanking marker, D11S4076, revealed two recombinations and the closest telomeric flanking marker, UGB, revealed one recombination. The recombinations have occurred in affected individuals, which eliminates the potential problem of reduced penetrance. The order and physical distance between 22 markers located at proximal 11q13 were analyzed on the G3 Stanford radiation-reduced cell hybrids. The data suggest that the VMD-2 region flanked by the microsatellite markers D11S4076 and UGB is approximately 980 kb.
Edwin M. Stone - One of the best experts on this subject based on the ideXlab platform.
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Differential Macular and peripheral expression of bestrophin in human eyes and its implication for best disease.
Investigative ophthalmology & visual science, 2007Co-Authors: Robert F. Mullins, Markus H. Kuehn, Elizabeth A. Faidley, Nasreen A. Syed, Edwin M. StoneAbstract:PURPOSE. Best disease, or Vitelliform Macular Degeneration, is an autosomal dominant form of Macular Degeneration that is caused by mutations in the gene encoding bestrophin. On clinical examination, Best disease is characterized by an elevated lesion beneath the neurosensory retina, resembling an egg yolk. The lesions in Best disease are primarily restricted to the macula, a small region of the retina responsible for central vision. The nature of the Vitelliform material and the reason the development of such lesions is usually restricted to the macula are two unsolved questions in the pathogenesis of this disorder. METHODS. The expression of bestrophin protein and mRNA was evaluated by immunohistochemistry, Western blot, and quantitative PCR in a series of normal human eyes. The ultrastructure of the retinal pigment epithelium and the histopathology of two donors with clinically diagnosed Best disease were also examined. RESULTS. An eye from a Best disease donor with a T6R mutation was found to have deposits containing lipid and glycoconjugates within the central retinal scar. These deposits may be remnants of the Vitelliform lesion. Immunohistochemical localization of bestrophin in a series of 22 unaffected eyes revealed a pattern in which Macular labeling was less robust than labeling outside the macula in most (18/22) cases. This pattern was confirmed using quantitative PCR and Western blotting. CONCLUSIONS. Topographic differences in the levels of bestrophin protein may in part explain the propensity for the macula to develop lesions in Best disease.
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Genetic linkage of Vitelliform Macular Degeneration (Best's disease) to chromosome 11q13
Nature Genetics, 1992Co-Authors: Edwin M. Stone, Brian E. Nichols, Luan M. Streb, Alan E. Kimura, Val C. SheffieldAbstract:Macular Degeneration is the most common cause of legal blindness in older patients in developed countries. Best's Vitelliform dystrophy is an early–onset, autosomal dominant form of Macular Degeneration characterized by an egg–yolk–like collection of lipofuscin beneath the pigment epithelium of the retinal macula. Fifty–seven members of a five–generation family affected with this disease were studied. A combination of ophthalmoscopy and electro–oculography was used for diagnosis; 29 patients were found to be affected and 16 unaffected. Linkage analysis mapped the disease–causing gene to chromosome 11q13. Three markers in this region were found to be significantly linked (Z_max > 3.0) to the disease. Multipoint analysis yielded a maximum Lod score of 9.3 in the interval between markers INT2 and D11S871 .
