The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
Travis J Hinson - One of the best experts on this subject based on the ideXlab platform.
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missense mutations in the bcs1l gene as a cause of the bjornstad syndrome
2007Co-Authors: Travis J Hinson, Valeria R Fantin, Jost Schonberger, Noralv Breivik, Geir Siem, Barbara Mcdonough, Pankaj Sharma, Ivan Keogh, Ricardo Neves GodinhoAbstract:BACKGROUND The Bjornstad syndrome, an autosomal recessive disorder associated with sensorineural hearing loss and Pili Torti, is caused by mutation of a previously unidentified gene on chromosome 2q34-36. METHODS Refined genetic mapping and DNA sequencing of 44 genes between D2S2210 and D2S2244 revealed BCS1L mutations. Functional analyses elucidated how BCS1L mutations cause the Bjornstad syndrome. RESULTS BCS1L encodes a member of the AAA family of ATPases that is necessary for the assembly of complex III in the mitochondria. In addition to the Bjornstad syndrome, BCS1L mutations cause complex III deficiency and the GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders. Patients with the Bjornstad syndrome have mutations that alter residues involved in protein-protein interactions, whereas mutations in patients with complex III deficiency alter ATP-binding residues, as deduced from the crystal structure of a related AAA-family ATPase. Biochemical studies provided evidence to support this model: complex III deficiency mutations prevented ATP-dependent assembly of BCS1L-associated complexes. All mutant BCS1L proteins disrupted the assembly of complex III, reduced the activity of the mitochondrial electron-transport chain, and increased the production of reactive oxygen species. However, only mutations associated with complex III deficiency increased mitochondrial content, which further increased the production of reactive oxygen species. CONCLUSIONS BCS1L mutations cause disease phenotypes ranging from highly restricted Pili Torti and sensorineural hearing loss (the Bjornstad syndrome) to profound multisystem organ failure (complex III deficiency and the GRACILE syndrome). All BCS1L mutations disrupted the assembly of mitochondrial respirasomes (the basic unit for respiration in human mitochondria), but the clinical expression of the mutations was correlated with the production of reactive oxygen species. Mutations that cause the Bjornstad syndrome illustrate the exquisite sensitivity of ear and hair tissues to mitochondrial function, particularly to the production of reactive oxygen species.
Albert David - One of the best experts on this subject based on the ideXlab platform.
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Novel Keratin 17 Mutations in Pachyonychia Congenita Type 2
2001Co-Authors: Frances J D Smith, Romano Tenconi, Carrie M. Coleman, Nagy M. Bayoumy, John Nelson, Albert DavidAbstract:Pachyonychia congenita type 2 is an inherited ectodermal dysplasia characterized by hypertrophic nail dystrophy and multiple pilosebaceous cysts. Focal nonepidermolytic palmoplantar keratoderma, natal teeth, and Pili Torti may also be present. Epithelial tissues affected in pachyonychia congenita type 2 express the keratin pair K6b/K17. Here, we report three novel heterozygous mutations in the K17 gene (KRT17A) in patients presenting with pachyonychia congenita type 2. These mutations, R94-98del (deletion of the peptide sequence RLASY) and missense mutations R94P and L95Q, are all within the 1A domain hotspot for pathogenic keratin mutations.
Barbara Mcdonough - One of the best experts on this subject based on the ideXlab platform.
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missense mutations in the bcs1l gene as a cause of the bjornstad syndrome
2007Co-Authors: Travis J Hinson, Valeria R Fantin, Jost Schonberger, Noralv Breivik, Geir Siem, Barbara Mcdonough, Pankaj Sharma, Ivan Keogh, Ricardo Neves GodinhoAbstract:BACKGROUND The Bjornstad syndrome, an autosomal recessive disorder associated with sensorineural hearing loss and Pili Torti, is caused by mutation of a previously unidentified gene on chromosome 2q34-36. METHODS Refined genetic mapping and DNA sequencing of 44 genes between D2S2210 and D2S2244 revealed BCS1L mutations. Functional analyses elucidated how BCS1L mutations cause the Bjornstad syndrome. RESULTS BCS1L encodes a member of the AAA family of ATPases that is necessary for the assembly of complex III in the mitochondria. In addition to the Bjornstad syndrome, BCS1L mutations cause complex III deficiency and the GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders. Patients with the Bjornstad syndrome have mutations that alter residues involved in protein-protein interactions, whereas mutations in patients with complex III deficiency alter ATP-binding residues, as deduced from the crystal structure of a related AAA-family ATPase. Biochemical studies provided evidence to support this model: complex III deficiency mutations prevented ATP-dependent assembly of BCS1L-associated complexes. All mutant BCS1L proteins disrupted the assembly of complex III, reduced the activity of the mitochondrial electron-transport chain, and increased the production of reactive oxygen species. However, only mutations associated with complex III deficiency increased mitochondrial content, which further increased the production of reactive oxygen species. CONCLUSIONS BCS1L mutations cause disease phenotypes ranging from highly restricted Pili Torti and sensorineural hearing loss (the Bjornstad syndrome) to profound multisystem organ failure (complex III deficiency and the GRACILE syndrome). All BCS1L mutations disrupted the assembly of mitochondrial respirasomes (the basic unit for respiration in human mitochondria), but the clinical expression of the mutations was correlated with the production of reactive oxygen species. Mutations that cause the Bjornstad syndrome illustrate the exquisite sensitivity of ear and hair tissues to mitochondrial function, particularly to the production of reactive oxygen species.
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The Bjornstad Syndrome (Sensorineural Hearing Loss and Pili Torti) Disease Gene Maps to Chromosome 2q34-36
1998Co-Authors: José Faibes Lubianca Neto, Barbara Mcdonough, Roland D. Eavey, Marco Antonio Macias Flores, Raul Martinez Caldera, Somkiat Sangwatanaroj, Jean-jacques Schott, Jose Ignatio Santos, Christine E. SeidmanAbstract:We report that the Bjornstad syndrome gene maps to chromosome 2q34-36. The clinical association of sensorineural hearing loss with Pili Torti (broken, twisted hairs) was described >30 years ago by Bjornstad; subsequently, several small families have been studied. We evaluated a large kindred with Bjornstad syndrome in which eight members inherited Pili Torti and prelingual sensorineural hearing loss as autosomal recessive traits. A genomewide search using polymorphic loci demonstrated linkage between the disease gene segregating in this kindred and D2S434 (maximum two-point LOD score = 4.98 at θ = 0). Haplotype analysis of recombination events located the disease gene in a 3-cM region between loci D2S1371 and D2S163. We speculate that intermediate filament and intermediate filament-associated proteins are good candidate genes for causing Bjornstad syndrome.
Ricardo Neves Godinho - One of the best experts on this subject based on the ideXlab platform.
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missense mutations in the bcs1l gene as a cause of the bjornstad syndrome
2007Co-Authors: Travis J Hinson, Valeria R Fantin, Jost Schonberger, Noralv Breivik, Geir Siem, Barbara Mcdonough, Pankaj Sharma, Ivan Keogh, Ricardo Neves GodinhoAbstract:BACKGROUND The Bjornstad syndrome, an autosomal recessive disorder associated with sensorineural hearing loss and Pili Torti, is caused by mutation of a previously unidentified gene on chromosome 2q34-36. METHODS Refined genetic mapping and DNA sequencing of 44 genes between D2S2210 and D2S2244 revealed BCS1L mutations. Functional analyses elucidated how BCS1L mutations cause the Bjornstad syndrome. RESULTS BCS1L encodes a member of the AAA family of ATPases that is necessary for the assembly of complex III in the mitochondria. In addition to the Bjornstad syndrome, BCS1L mutations cause complex III deficiency and the GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders. Patients with the Bjornstad syndrome have mutations that alter residues involved in protein-protein interactions, whereas mutations in patients with complex III deficiency alter ATP-binding residues, as deduced from the crystal structure of a related AAA-family ATPase. Biochemical studies provided evidence to support this model: complex III deficiency mutations prevented ATP-dependent assembly of BCS1L-associated complexes. All mutant BCS1L proteins disrupted the assembly of complex III, reduced the activity of the mitochondrial electron-transport chain, and increased the production of reactive oxygen species. However, only mutations associated with complex III deficiency increased mitochondrial content, which further increased the production of reactive oxygen species. CONCLUSIONS BCS1L mutations cause disease phenotypes ranging from highly restricted Pili Torti and sensorineural hearing loss (the Bjornstad syndrome) to profound multisystem organ failure (complex III deficiency and the GRACILE syndrome). All BCS1L mutations disrupted the assembly of mitochondrial respirasomes (the basic unit for respiration in human mitochondria), but the clinical expression of the mutations was correlated with the production of reactive oxygen species. Mutations that cause the Bjornstad syndrome illustrate the exquisite sensitivity of ear and hair tissues to mitochondrial function, particularly to the production of reactive oxygen species.
Christine E. Seidman - One of the best experts on this subject based on the ideXlab platform.
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The Bjornstad Syndrome (Sensorineural Hearing Loss and Pili Torti) Disease Gene Maps to Chromosome 2q34-36
1998Co-Authors: José Faibes Lubianca Neto, Barbara Mcdonough, Roland D. Eavey, Marco Antonio Macias Flores, Raul Martinez Caldera, Somkiat Sangwatanaroj, Jean-jacques Schott, Jose Ignatio Santos, Christine E. SeidmanAbstract:We report that the Bjornstad syndrome gene maps to chromosome 2q34-36. The clinical association of sensorineural hearing loss with Pili Torti (broken, twisted hairs) was described >30 years ago by Bjornstad; subsequently, several small families have been studied. We evaluated a large kindred with Bjornstad syndrome in which eight members inherited Pili Torti and prelingual sensorineural hearing loss as autosomal recessive traits. A genomewide search using polymorphic loci demonstrated linkage between the disease gene segregating in this kindred and D2S434 (maximum two-point LOD score = 4.98 at θ = 0). Haplotype analysis of recombination events located the disease gene in a 3-cM region between loci D2S1371 and D2S163. We speculate that intermediate filament and intermediate filament-associated proteins are good candidate genes for causing Bjornstad syndrome.