The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Francis L Munier - One of the best experts on this subject based on the ideXlab platform.
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a dominant mutation within the dna binding domain of the bzip Transcription Factor Maf causes murine cataract and results in selective alteration in dna binding
Human Molecular Genetics, 2003Co-Authors: Mary F Lyon, Robyn V Jamieson, Rahat Perveen, P H Glenister, Robert Griffiths, Yvonne Boyd, Laurie H Glimcher, J Favor, Francis L Munier, Graeme C M BlackAbstract:The murine autosomal dominant cataract mutants created in mutagenesis experiments have proven to be a powerful resource for modelling the biological processes involved in cataractogenesis. We report a mutant which in the heterozygous state exhibits mild pulverulent cataract named 'opaque flecks in lens', symbol Ofl. By molecular mapping, followed by a candidate gene approach, the mutant was shown to be allelic with a knockout of the bZIP Transcription Factor, Maf. Homozygotes for Ofl and for Maf null mutations are similar but a new effect, renal tubular nephritis, was found in Ofl homozygotes surviving beyond 4 weeks, which may contribute to early lethality. Sequencing identified the mutation as a G-->A change, leading to the amino-acid substitution mutation R291Q in the basic region of the DNA-binding domain. Since mice heterozygous for knockouts of Maf show no cataracts, this suggests that the Ofl R291Q mutant protein has a dominant effect. We have demonstrated that this mutation results in a selective alteration in DNA binding affinities to target oligonucleotides containing variations in the core CRE and TRE elements. This implies that arginine 291 is important for core element binding and suggests that the mutant protein may exert a differential downstream effect amongst its binding targets. The cataracts seen in Ofl heterozygotes and human Maf mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract. Furthermore, when bred onto a different genetic background Ofl heterozygotes also show anterior segment abnormalities. The Ofl mutant therefore provides a valuable model system for the study of Maf, and its interacting Factors, in normal and abnormal lens and anterior segment development.
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domain disruption and mutation of the bzip Transcription Factor Maf associated with cataract ocular anterior segment dysgenesis and coloboma
Human Molecular Genetics, 2002Co-Authors: Robyn V Jamieson, Rahat Perveen, Bronwyn Kerr, Martin Carette, Jill Yardley, Elise Heon, Gabriela M Wirth, Veronica Van Heyningen, Di Donnai, Francis L MunierAbstract:Human congenital cataract and ocular anterior segment dysgenesis both demonstrate extensive genetic and phenotypic heterogeneity. We identified a family where ocular developmental abnormalities (cataract, anterior segment dysgenesis and microphthalmia) co-segregated with a translocation, t(5;16)(p15.3;q23.2), in both balanced and unbalanced forms. We hypothesized that this altered the expression of a gene of developmental significance in the human lens and ocular anterior segment. Cloning the 16q23.2 breakpoint demonstrated that it transected the genomic-control domain of Maf, a basic region leucine zipper (bZIP) Transcription Factor, first identified as an oncogene, which is expressed in vertebrate lens development and regulates the expression of the eye lens crystallins. The homozygous null mutant Maf mouse embryo demonstrates defective lens formation and microphthalmia. Through mutation screening of a panel of patients with hereditary congenital cataract we identified a mutation in Maf in a three-generation family with cataract, microcornea and iris coloboma. The mutation results in the substitution of an evolutionarily highly conserved arginine with a proline at residue 288 (R288P) in the basic region of the DNA-binding domain of Maf. Our findings further implicate Maf/Maf in mammalian lens development and highlight the role of the lens in anterior segment development. The 16q23.2 breakpoint transects the common fragile site, FRA16D, providing a molecular demonstration of a germline break in a common fragile site.
Robyn V Jamieson - One of the best experts on this subject based on the ideXlab platform.
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pulverulent cataract with variably associated microcornea and iris coloboma in a Maf mutation family
British Journal of Ophthalmology, 2003Co-Authors: Robyn V Jamieson, F L Munier, A Balmer, N Farrar, Rahat Perveen, Graeme C M BlackAbstract:Aims: To report the detailed clinical findings in a three generation pedigree with autosomal dominant cataract, microcornea, and coloboma resulting from mutation of the lens development gene, Maf. Methods: Five members of a three generation pedigree with progressive cataracts underwent detailed ophthalmic examination to characterise associated ocular phenotypic features. Results: The cataracts present in all affected individuals were cortical, and/or nuclear, pulverulent opacities. Corneal diameters of 10–10.25 mm were present in two family members. Axial lengths were in the normal range. Bilateral iris coloboma in the 6 o'clock position was present in one patient. Uveal melanoma was present in one patient, with uveal naevi in this and one other patient. Conclusion: The bZIP Transcription Factor Maf is a key lens development gene that regulates the expression of the crystallins. Individuals with a mutation in Maf may have pulverulent cataract alone or cataract in association with microcornea or iris coloboma.
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a dominant mutation within the dna binding domain of the bzip Transcription Factor Maf causes murine cataract and results in selective alteration in dna binding
Human Molecular Genetics, 2003Co-Authors: Mary F Lyon, Robyn V Jamieson, Rahat Perveen, P H Glenister, Robert Griffiths, Yvonne Boyd, Laurie H Glimcher, J Favor, Francis L Munier, Graeme C M BlackAbstract:The murine autosomal dominant cataract mutants created in mutagenesis experiments have proven to be a powerful resource for modelling the biological processes involved in cataractogenesis. We report a mutant which in the heterozygous state exhibits mild pulverulent cataract named 'opaque flecks in lens', symbol Ofl. By molecular mapping, followed by a candidate gene approach, the mutant was shown to be allelic with a knockout of the bZIP Transcription Factor, Maf. Homozygotes for Ofl and for Maf null mutations are similar but a new effect, renal tubular nephritis, was found in Ofl homozygotes surviving beyond 4 weeks, which may contribute to early lethality. Sequencing identified the mutation as a G-->A change, leading to the amino-acid substitution mutation R291Q in the basic region of the DNA-binding domain. Since mice heterozygous for knockouts of Maf show no cataracts, this suggests that the Ofl R291Q mutant protein has a dominant effect. We have demonstrated that this mutation results in a selective alteration in DNA binding affinities to target oligonucleotides containing variations in the core CRE and TRE elements. This implies that arginine 291 is important for core element binding and suggests that the mutant protein may exert a differential downstream effect amongst its binding targets. The cataracts seen in Ofl heterozygotes and human Maf mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract. Furthermore, when bred onto a different genetic background Ofl heterozygotes also show anterior segment abnormalities. The Ofl mutant therefore provides a valuable model system for the study of Maf, and its interacting Factors, in normal and abnormal lens and anterior segment development.
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domain disruption and mutation of the bzip Transcription Factor Maf associated with cataract ocular anterior segment dysgenesis and coloboma
Human Molecular Genetics, 2002Co-Authors: Robyn V Jamieson, Rahat Perveen, Bronwyn Kerr, Martin Carette, Jill Yardley, Elise Heon, Gabriela M Wirth, Veronica Van Heyningen, Di Donnai, Francis L MunierAbstract:Human congenital cataract and ocular anterior segment dysgenesis both demonstrate extensive genetic and phenotypic heterogeneity. We identified a family where ocular developmental abnormalities (cataract, anterior segment dysgenesis and microphthalmia) co-segregated with a translocation, t(5;16)(p15.3;q23.2), in both balanced and unbalanced forms. We hypothesized that this altered the expression of a gene of developmental significance in the human lens and ocular anterior segment. Cloning the 16q23.2 breakpoint demonstrated that it transected the genomic-control domain of Maf, a basic region leucine zipper (bZIP) Transcription Factor, first identified as an oncogene, which is expressed in vertebrate lens development and regulates the expression of the eye lens crystallins. The homozygous null mutant Maf mouse embryo demonstrates defective lens formation and microphthalmia. Through mutation screening of a panel of patients with hereditary congenital cataract we identified a mutation in Maf in a three-generation family with cataract, microcornea and iris coloboma. The mutation results in the substitution of an evolutionarily highly conserved arginine with a proline at residue 288 (R288P) in the basic region of the DNA-binding domain of Maf. Our findings further implicate Maf/Maf in mammalian lens development and highlight the role of the lens in anterior segment development. The 16q23.2 breakpoint transects the common fragile site, FRA16D, providing a molecular demonstration of a germline break in a common fragile site.
Rahat Perveen - One of the best experts on this subject based on the ideXlab platform.
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pulverulent cataract with variably associated microcornea and iris coloboma in a Maf mutation family
British Journal of Ophthalmology, 2003Co-Authors: Robyn V Jamieson, F L Munier, A Balmer, N Farrar, Rahat Perveen, Graeme C M BlackAbstract:Aims: To report the detailed clinical findings in a three generation pedigree with autosomal dominant cataract, microcornea, and coloboma resulting from mutation of the lens development gene, Maf. Methods: Five members of a three generation pedigree with progressive cataracts underwent detailed ophthalmic examination to characterise associated ocular phenotypic features. Results: The cataracts present in all affected individuals were cortical, and/or nuclear, pulverulent opacities. Corneal diameters of 10–10.25 mm were present in two family members. Axial lengths were in the normal range. Bilateral iris coloboma in the 6 o'clock position was present in one patient. Uveal melanoma was present in one patient, with uveal naevi in this and one other patient. Conclusion: The bZIP Transcription Factor Maf is a key lens development gene that regulates the expression of the crystallins. Individuals with a mutation in Maf may have pulverulent cataract alone or cataract in association with microcornea or iris coloboma.
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a dominant mutation within the dna binding domain of the bzip Transcription Factor Maf causes murine cataract and results in selective alteration in dna binding
Human Molecular Genetics, 2003Co-Authors: Mary F Lyon, Robyn V Jamieson, Rahat Perveen, P H Glenister, Robert Griffiths, Yvonne Boyd, Laurie H Glimcher, J Favor, Francis L Munier, Graeme C M BlackAbstract:The murine autosomal dominant cataract mutants created in mutagenesis experiments have proven to be a powerful resource for modelling the biological processes involved in cataractogenesis. We report a mutant which in the heterozygous state exhibits mild pulverulent cataract named 'opaque flecks in lens', symbol Ofl. By molecular mapping, followed by a candidate gene approach, the mutant was shown to be allelic with a knockout of the bZIP Transcription Factor, Maf. Homozygotes for Ofl and for Maf null mutations are similar but a new effect, renal tubular nephritis, was found in Ofl homozygotes surviving beyond 4 weeks, which may contribute to early lethality. Sequencing identified the mutation as a G-->A change, leading to the amino-acid substitution mutation R291Q in the basic region of the DNA-binding domain. Since mice heterozygous for knockouts of Maf show no cataracts, this suggests that the Ofl R291Q mutant protein has a dominant effect. We have demonstrated that this mutation results in a selective alteration in DNA binding affinities to target oligonucleotides containing variations in the core CRE and TRE elements. This implies that arginine 291 is important for core element binding and suggests that the mutant protein may exert a differential downstream effect amongst its binding targets. The cataracts seen in Ofl heterozygotes and human Maf mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract. Furthermore, when bred onto a different genetic background Ofl heterozygotes also show anterior segment abnormalities. The Ofl mutant therefore provides a valuable model system for the study of Maf, and its interacting Factors, in normal and abnormal lens and anterior segment development.
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domain disruption and mutation of the bzip Transcription Factor Maf associated with cataract ocular anterior segment dysgenesis and coloboma
Human Molecular Genetics, 2002Co-Authors: Robyn V Jamieson, Rahat Perveen, Bronwyn Kerr, Martin Carette, Jill Yardley, Elise Heon, Gabriela M Wirth, Veronica Van Heyningen, Di Donnai, Francis L MunierAbstract:Human congenital cataract and ocular anterior segment dysgenesis both demonstrate extensive genetic and phenotypic heterogeneity. We identified a family where ocular developmental abnormalities (cataract, anterior segment dysgenesis and microphthalmia) co-segregated with a translocation, t(5;16)(p15.3;q23.2), in both balanced and unbalanced forms. We hypothesized that this altered the expression of a gene of developmental significance in the human lens and ocular anterior segment. Cloning the 16q23.2 breakpoint demonstrated that it transected the genomic-control domain of Maf, a basic region leucine zipper (bZIP) Transcription Factor, first identified as an oncogene, which is expressed in vertebrate lens development and regulates the expression of the eye lens crystallins. The homozygous null mutant Maf mouse embryo demonstrates defective lens formation and microphthalmia. Through mutation screening of a panel of patients with hereditary congenital cataract we identified a mutation in Maf in a three-generation family with cataract, microcornea and iris coloboma. The mutation results in the substitution of an evolutionarily highly conserved arginine with a proline at residue 288 (R288P) in the basic region of the DNA-binding domain of Maf. Our findings further implicate Maf/Maf in mammalian lens development and highlight the role of the lens in anterior segment development. The 16q23.2 breakpoint transects the common fragile site, FRA16D, providing a molecular demonstration of a germline break in a common fragile site.
Graeme C M Black - One of the best experts on this subject based on the ideXlab platform.
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pulverulent cataract with variably associated microcornea and iris coloboma in a Maf mutation family
British Journal of Ophthalmology, 2003Co-Authors: Robyn V Jamieson, F L Munier, A Balmer, N Farrar, Rahat Perveen, Graeme C M BlackAbstract:Aims: To report the detailed clinical findings in a three generation pedigree with autosomal dominant cataract, microcornea, and coloboma resulting from mutation of the lens development gene, Maf. Methods: Five members of a three generation pedigree with progressive cataracts underwent detailed ophthalmic examination to characterise associated ocular phenotypic features. Results: The cataracts present in all affected individuals were cortical, and/or nuclear, pulverulent opacities. Corneal diameters of 10–10.25 mm were present in two family members. Axial lengths were in the normal range. Bilateral iris coloboma in the 6 o'clock position was present in one patient. Uveal melanoma was present in one patient, with uveal naevi in this and one other patient. Conclusion: The bZIP Transcription Factor Maf is a key lens development gene that regulates the expression of the crystallins. Individuals with a mutation in Maf may have pulverulent cataract alone or cataract in association with microcornea or iris coloboma.
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a dominant mutation within the dna binding domain of the bzip Transcription Factor Maf causes murine cataract and results in selective alteration in dna binding
Human Molecular Genetics, 2003Co-Authors: Mary F Lyon, Robyn V Jamieson, Rahat Perveen, P H Glenister, Robert Griffiths, Yvonne Boyd, Laurie H Glimcher, J Favor, Francis L Munier, Graeme C M BlackAbstract:The murine autosomal dominant cataract mutants created in mutagenesis experiments have proven to be a powerful resource for modelling the biological processes involved in cataractogenesis. We report a mutant which in the heterozygous state exhibits mild pulverulent cataract named 'opaque flecks in lens', symbol Ofl. By molecular mapping, followed by a candidate gene approach, the mutant was shown to be allelic with a knockout of the bZIP Transcription Factor, Maf. Homozygotes for Ofl and for Maf null mutations are similar but a new effect, renal tubular nephritis, was found in Ofl homozygotes surviving beyond 4 weeks, which may contribute to early lethality. Sequencing identified the mutation as a G-->A change, leading to the amino-acid substitution mutation R291Q in the basic region of the DNA-binding domain. Since mice heterozygous for knockouts of Maf show no cataracts, this suggests that the Ofl R291Q mutant protein has a dominant effect. We have demonstrated that this mutation results in a selective alteration in DNA binding affinities to target oligonucleotides containing variations in the core CRE and TRE elements. This implies that arginine 291 is important for core element binding and suggests that the mutant protein may exert a differential downstream effect amongst its binding targets. The cataracts seen in Ofl heterozygotes and human Maf mutations are similar to one another, implying that Ofl may be a model of human pulverulent cortical cataract. Furthermore, when bred onto a different genetic background Ofl heterozygotes also show anterior segment abnormalities. The Ofl mutant therefore provides a valuable model system for the study of Maf, and its interacting Factors, in normal and abnormal lens and anterior segment development.
Di Donnai - One of the best experts on this subject based on the ideXlab platform.
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Domain disruption and mutation of the bZIP Transcription Factor, Maf,associated with cataract, ocular anterior segment dysgenesis and coloboma
2017Co-Authors: Jamieson Robyn, Di Donnai, Perveen Rahat, Kerr Bronwyn, Carette Martin, Yardley Jill, Heon Elise, Wirth M. Gabriela, Van Heyningen Veronica, Munier FrancisAbstract:Human congenital cataract and ocular anterior segment dysgenesis both demonstrate extensive genetic and phenotypic heterogeneity. We identified a family where ocular developmental abnormalities (cataract, anterior segment dysgenesis and microphthalmia) co-segregated with a translocation, t(5;16)(p15.3;q23.2), in both balanced and unbalanced forms. We hypothesized that this altered the expression of a gene of developmental significance in the human lens and ocular anterior segment. Cloning the 16q23.2 breakpoint demonstrated that it transected the genomic-control domain of Maf, a basic region leucine zipper (bZIP) Transcription Factor, first identified as an oncogene, which is expressed in vertebrate lens development and regulates the expression of the eye lens crystallins. The homozygous null mutant Maf mouse embryo demonstrates defective lens formation and microphthalmia. Through mutation screening of a panel of patients with hereditary congenital cataract we identified a mutation in Maf in a three-generation family with cataract, microcornea and iris coloboma. The mutation results in the substitution of an evolutionarily highly conserved arginine with a proline at residue 288 (R288P) in the basic region of the DNA-binding domain of Maf. Our findings further implicate Maf/Maf in mammalian lens development and highlight the role of the lens in anterior segment development. The 16q23.2 breakpoint transects the common fragile site, FRA16D, providing a molecular demonstration of a germline break in a common fragile sit
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domain disruption and mutation of the bzip Transcription Factor Maf associated with cataract ocular anterior segment dysgenesis and coloboma
Human Molecular Genetics, 2002Co-Authors: Robyn V Jamieson, Rahat Perveen, Bronwyn Kerr, Martin Carette, Jill Yardley, Elise Heon, Gabriela M Wirth, Veronica Van Heyningen, Di Donnai, Francis L MunierAbstract:Human congenital cataract and ocular anterior segment dysgenesis both demonstrate extensive genetic and phenotypic heterogeneity. We identified a family where ocular developmental abnormalities (cataract, anterior segment dysgenesis and microphthalmia) co-segregated with a translocation, t(5;16)(p15.3;q23.2), in both balanced and unbalanced forms. We hypothesized that this altered the expression of a gene of developmental significance in the human lens and ocular anterior segment. Cloning the 16q23.2 breakpoint demonstrated that it transected the genomic-control domain of Maf, a basic region leucine zipper (bZIP) Transcription Factor, first identified as an oncogene, which is expressed in vertebrate lens development and regulates the expression of the eye lens crystallins. The homozygous null mutant Maf mouse embryo demonstrates defective lens formation and microphthalmia. Through mutation screening of a panel of patients with hereditary congenital cataract we identified a mutation in Maf in a three-generation family with cataract, microcornea and iris coloboma. The mutation results in the substitution of an evolutionarily highly conserved arginine with a proline at residue 288 (R288P) in the basic region of the DNA-binding domain of Maf. Our findings further implicate Maf/Maf in mammalian lens development and highlight the role of the lens in anterior segment development. The 16q23.2 breakpoint transects the common fragile site, FRA16D, providing a molecular demonstration of a germline break in a common fragile site.