The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Peter H Byers - One of the best experts on this subject based on the ideXlab platform.
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Osteogenesis Imperfecta a translational approach to brittle bone disease
2013Co-Authors: Jay R. Shapiro, Francis H Glorieux, Peter H Byers, Paul SponsellorAbstract:Osteogenesis Imperfecta is the first translational reference professionals can turn to for a source of comprehensive information on this disorder. Although several reviews of the field have been published in various journals, there is no other single source for a compendium of current information. Separate chapters discuss each of the several clinical features of OI. Ethical issues related to OI are discussed, as is the importance of nutrition in managing the OI child and the OI adult. The role of physical medicine and rehabilitation for OI patients is also presented, along with the current status of OI medical treatment and the prospects for genetic engineering in the future. The text also provides the orthopedic surgeon with an advanced discussion of surgical techniques applicable to OI. Incorporates chapters and information on the ethical issues related to Osteogenesis Imperfecta (OI) as will the importance of nutrition in managing the OI child and the OI adult Offers new insights into the underlying mechanisms of collagen biochemistry as related to OI as well as a presentation of intracellular collagen processing and the expanded role of protein chaperones in OI Discusses the role of physical medicine and rehabilitation for OI patients and the current status of OI medical treatment as well as prospects for genetic engineering in the future Provides a unique overview for the orthopedic surgeon with an advanced discussion of surgical techniques applicable to OI
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recessively inherited forms of Osteogenesis Imperfecta
Annual Review of Genetics, 2012Co-Authors: Peter H Byers, Shawna M PyottAbstract:More than 90% of people who have Osteogenesis Imperfecta (OI) have heterozygous mutations in one of the two type I collagen genes, COL1A1 and COL1A2. The effects of these changes range from death in the perinatal period to barely increased fracture frequency and reflect different types of mutations. Introduction of bisphosphonates during the past 20 years has targeted bone fragility by decreased resorption. The recent recognition of biallelic mutations in genes that affect either collagen assembly and processing or the regulation of osteoblast development has raised hopes for therapies that would be specific for single-gene disorders and identify cellular targets in individuals with the dominant forms of OI. These hopes are yet to be met, but the study of the recessively inherited forms of OI has illuminated the details of the collagen processing pathways.
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Recurrence of perinatal lethal Osteogenesis Imperfecta in sibships: Parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Purpose: Recurrence of lethal Osteogenesis Imperfecta in families results from either dominant (parental mosaicism) or recessive inheritance. The proportion of these two mechanisms is not known, and determination of the contribution of each is important to structure genetic counseling for these families. Methods: We measured the recurrence rate of lethal Osteogenesis Imperfecta after the birth of an affected infant. We determined the rate of parental mosaicism in a subset of families in which we had identified dominant mutations. In 37 families in which two or more affected infants were born, we identified mutations and determined the proportion that resulted from recessive inheritance. Results: The recurrence rate after the first affected pregnancy was 1.3%. The rate of parental mosaicism in families in which a dominant mutation was identified in a first affected child was 16%. In 37 families with two affected infants, 26 had dominant mutations, seven had recessive mutations, and we failed to find mutations in four. The overall recurrence rate for couples after two or more affected infants was 32%; 27% for families with parental mosaicism, 31% for recessive mutations, and 50% for families with no identified mutation. Conclusions: In most populations, recurrence of lethal Osteogenesis Imperfecta usually results from parental mosaicism for dominant mutations, but the carrier frequency of recessive forms of Osteogenesis Imperfecta will alter that proportion. Mutation identification is an important tool to assess risk and facilitate prenatal or preimplantation diagnosis.
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gene targeting in stem cells from individuals with Osteogenesis Imperfecta
Science, 2004Co-Authors: Joel R Chamberlain, Ulrike Schwarze, Michael D Sussman, Pei Rong Wang, Roli K Hirata, Kurt D Hankenson, James M Pace, Robert A Underwood, Kit M Song, Peter H ByersAbstract:Adult stem cells offer the potential to treat many diseases through a combination of ex vivo genetic manipulation and autologous transplantation. Mesenchymal stem cells (MSCs, also referred to as marrow stromal cells) are adult stem cells that can be isolated as proliferating, adherent cells from bones. MSCs can differentiate into multiple cell types present in several tissues, including bone, fat, cartilage, and muscle, making them ideal candidates for a variety of cell-based therapies. Here, we have used adeno-associated virus vectors to disrupt dominant-negative mutant COL1A1 collagen genes in MSCs from individuals with the brittle bone disorder Osteogenesis Imperfecta, demonstrating successful gene targeting in adult human stem cells.
Shawna M Pyott - One of the best experts on this subject based on the ideXlab platform.
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recessively inherited forms of Osteogenesis Imperfecta
Annual Review of Genetics, 2012Co-Authors: Peter H Byers, Shawna M PyottAbstract:More than 90% of people who have Osteogenesis Imperfecta (OI) have heterozygous mutations in one of the two type I collagen genes, COL1A1 and COL1A2. The effects of these changes range from death in the perinatal period to barely increased fracture frequency and reflect different types of mutations. Introduction of bisphosphonates during the past 20 years has targeted bone fragility by decreased resorption. The recent recognition of biallelic mutations in genes that affect either collagen assembly and processing or the regulation of osteoblast development has raised hopes for therapies that would be specific for single-gene disorders and identify cellular targets in individuals with the dominant forms of OI. These hopes are yet to be met, but the study of the recessively inherited forms of OI has illuminated the details of the collagen processing pathways.
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Recurrence of perinatal lethal Osteogenesis Imperfecta in sibships: Parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Purpose: Recurrence of lethal Osteogenesis Imperfecta in families results from either dominant (parental mosaicism) or recessive inheritance. The proportion of these two mechanisms is not known, and determination of the contribution of each is important to structure genetic counseling for these families. Methods: We measured the recurrence rate of lethal Osteogenesis Imperfecta after the birth of an affected infant. We determined the rate of parental mosaicism in a subset of families in which we had identified dominant mutations. In 37 families in which two or more affected infants were born, we identified mutations and determined the proportion that resulted from recessive inheritance. Results: The recurrence rate after the first affected pregnancy was 1.3%. The rate of parental mosaicism in families in which a dominant mutation was identified in a first affected child was 16%. In 37 families with two affected infants, 26 had dominant mutations, seven had recessive mutations, and we failed to find mutations in four. The overall recurrence rate for couples after two or more affected infants was 32%; 27% for families with parental mosaicism, 31% for recessive mutations, and 50% for families with no identified mutation. Conclusions: In most populations, recurrence of lethal Osteogenesis Imperfecta usually results from parental mosaicism for dominant mutations, but the carrier frequency of recessive forms of Osteogenesis Imperfecta will alter that proportion. Mutation identification is an important tool to assess risk and facilitate prenatal or preimplantation diagnosis.
Ulrike Schwarze - One of the best experts on this subject based on the ideXlab platform.
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Recurrence of perinatal lethal Osteogenesis Imperfecta in sibships: Parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Purpose: Recurrence of lethal Osteogenesis Imperfecta in families results from either dominant (parental mosaicism) or recessive inheritance. The proportion of these two mechanisms is not known, and determination of the contribution of each is important to structure genetic counseling for these families. Methods: We measured the recurrence rate of lethal Osteogenesis Imperfecta after the birth of an affected infant. We determined the rate of parental mosaicism in a subset of families in which we had identified dominant mutations. In 37 families in which two or more affected infants were born, we identified mutations and determined the proportion that resulted from recessive inheritance. Results: The recurrence rate after the first affected pregnancy was 1.3%. The rate of parental mosaicism in families in which a dominant mutation was identified in a first affected child was 16%. In 37 families with two affected infants, 26 had dominant mutations, seven had recessive mutations, and we failed to find mutations in four. The overall recurrence rate for couples after two or more affected infants was 32%; 27% for families with parental mosaicism, 31% for recessive mutations, and 50% for families with no identified mutation. Conclusions: In most populations, recurrence of lethal Osteogenesis Imperfecta usually results from parental mosaicism for dominant mutations, but the carrier frequency of recessive forms of Osteogenesis Imperfecta will alter that proportion. Mutation identification is an important tool to assess risk and facilitate prenatal or preimplantation diagnosis.
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gene targeting in stem cells from individuals with Osteogenesis Imperfecta
Science, 2004Co-Authors: Joel R Chamberlain, Ulrike Schwarze, Michael D Sussman, Pei Rong Wang, Roli K Hirata, Kurt D Hankenson, James M Pace, Robert A Underwood, Kit M Song, Peter H ByersAbstract:Adult stem cells offer the potential to treat many diseases through a combination of ex vivo genetic manipulation and autologous transplantation. Mesenchymal stem cells (MSCs, also referred to as marrow stromal cells) are adult stem cells that can be isolated as proliferating, adherent cells from bones. MSCs can differentiate into multiple cell types present in several tissues, including bone, fat, cartilage, and muscle, making them ideal candidates for a variety of cell-based therapies. Here, we have used adeno-associated virus vectors to disrupt dominant-negative mutant COL1A1 collagen genes in MSCs from individuals with the brittle bone disorder Osteogenesis Imperfecta, demonstrating successful gene targeting in adult human stem cells.
Gretchen Smith - One of the best experts on this subject based on the ideXlab platform.
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Recurrence of perinatal lethal Osteogenesis Imperfecta in sibships: Parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Purpose: Recurrence of lethal Osteogenesis Imperfecta in families results from either dominant (parental mosaicism) or recessive inheritance. The proportion of these two mechanisms is not known, and determination of the contribution of each is important to structure genetic counseling for these families. Methods: We measured the recurrence rate of lethal Osteogenesis Imperfecta after the birth of an affected infant. We determined the rate of parental mosaicism in a subset of families in which we had identified dominant mutations. In 37 families in which two or more affected infants were born, we identified mutations and determined the proportion that resulted from recessive inheritance. Results: The recurrence rate after the first affected pregnancy was 1.3%. The rate of parental mosaicism in families in which a dominant mutation was identified in a first affected child was 16%. In 37 families with two affected infants, 26 had dominant mutations, seven had recessive mutations, and we failed to find mutations in four. The overall recurrence rate for couples after two or more affected infants was 32%; 27% for families with parental mosaicism, 31% for recessive mutations, and 50% for families with no identified mutation. Conclusions: In most populations, recurrence of lethal Osteogenesis Imperfecta usually results from parental mosaicism for dominant mutations, but the carrier frequency of recessive forms of Osteogenesis Imperfecta will alter that proportion. Mutation identification is an important tool to assess risk and facilitate prenatal or preimplantation diagnosis.
Melanie Pepin - One of the best experts on this subject based on the ideXlab platform.
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Recurrence of perinatal lethal Osteogenesis Imperfecta in sibships: Parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
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recurrence of perinatal lethal Osteogenesis Imperfecta in sibships parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance
Genetics in Medicine, 2011Co-Authors: Shawna M Pyott, Melanie Pepin, Ulrike Schwarze, Kathleen Yang, Gretchen Smith, Peter H ByersAbstract:Purpose: Recurrence of lethal Osteogenesis Imperfecta in families results from either dominant (parental mosaicism) or recessive inheritance. The proportion of these two mechanisms is not known, and determination of the contribution of each is important to structure genetic counseling for these families. Methods: We measured the recurrence rate of lethal Osteogenesis Imperfecta after the birth of an affected infant. We determined the rate of parental mosaicism in a subset of families in which we had identified dominant mutations. In 37 families in which two or more affected infants were born, we identified mutations and determined the proportion that resulted from recessive inheritance. Results: The recurrence rate after the first affected pregnancy was 1.3%. The rate of parental mosaicism in families in which a dominant mutation was identified in a first affected child was 16%. In 37 families with two affected infants, 26 had dominant mutations, seven had recessive mutations, and we failed to find mutations in four. The overall recurrence rate for couples after two or more affected infants was 32%; 27% for families with parental mosaicism, 31% for recessive mutations, and 50% for families with no identified mutation. Conclusions: In most populations, recurrence of lethal Osteogenesis Imperfecta usually results from parental mosaicism for dominant mutations, but the carrier frequency of recessive forms of Osteogenesis Imperfecta will alter that proportion. Mutation identification is an important tool to assess risk and facilitate prenatal or preimplantation diagnosis.
