FIRST OBSERVATION OF TUBB1 GENE MUTATIONS IN TURKISH PATIENTS WITH MACROTHROMBOCYTOPENIA
(Abstract release date: 05/19/16)
EHA Library. Ozkan D. 06/09/16; 132972; E1423
Dr. Didem Torun Ozkan
Contributions
Contributions
Abstract
Abstract: E1423
Type: Eposter Presentation
Background
Frequency of the rare bleeding disorders (RBDs) in the general population ranges from 1:500.000 to 1:2 millions. In countries with a high rate of consanguineous marriages RBDs occur more frequently, representing a significant clinical and social problem. Macrothrombocytopenia (giant platelet syndrome) is an autosomal dominant disorder and previous studies have demonstrated that Myosin Heavy Chain 9 (MYH9) mutations lead to this disorder. The pathogenesis of almost the half of diseases related to MYH9 gene is unknown. So its diagnosis is not possible. The membrane skeleton and the link between actin filaments of skeleton and microtubules contain the normal platelet morphology. The defects occurred on these systems results with macrothrombocytopenia. The relation between macrothrombocytopenia and the defect occurred on microtubules that consisted by alpha and beta tubulin heterodimers can be explained by the defect occurred on Tubulin Beta 1 (TUBB1) gene.According to HGMD (Human Gene Mutation Database) data; 52 mutations are defined in MYH9 gene between 2004 - 2014. 17 of these mutations are defined in patients with giant thrombocyte syndrome(macrothrombocytopenia). Only 2 mutations are defined related to TUBB1 gene, so the researches done on relation between TUBB1 and macrothrombocytopenia is limited. The guiding indicators on the treatment of this disease can be achieved in case of defining the effects of TUBB1 mutations on megakaryocytes-microtubule organization, proplatelet formation and platelet morphology
Aims
In this study, we aimed to analyze TUBB1 gene at Turkish population with clinically diagnosed macrothrombocytopenia.
Methods
A written informed consent for genetic analysis was obtained from the patients. The patient blood was collected from various hematology clinics in Turkey. In this study, TUBB1 gene mutation analysis was performed by using the blood of patients diagnosed with macrothrombocytopenia following the DNA isolation. Then samples were sequenced using a DNA sequencer (Beckman Coulter, USA). Sequencing are evaluated using with FinchTV program.
Results
TUBB1 gene analysis of Turkish patients with macrothrombocytopenia revealed a novel heterozygous Cytosine to Timin nucleotide change at 821 at exon4 (p.T274M/ Threonin to Methionine), at a child and his father in the same family, 99 nucleotide ahead which is at nucleotid 920, there is a novel heterozygous Guanine to Adenin nucleotide change, this situation caused to change of Arginine aminoacid to Histidine aminoacid at 307 position (p.R307H) in protein. These changes are conserved at evolutionary process, so we can say that these transitions are novel mutations. We also identified a double base pair substitution at nucleotide positions 130-131 at exon 2,this transition encodes the Q43P (p.Gly43Pro, p.Gly43His) mutant form of the protein. (nucleotide and aminoacid numbering as per m RNA GenBank entry NM_758664)
Conclusion
In this study, we identified the first TUBB1 mutation; combined 821C>T and 920 G>A mutations in a family and these mutations are not defined previously in Human Gene Mutation Database (HGMD). And Q43P single nucleotide polymorphism is defined firstly at Turkish population, so they are very important findings in terms of explaining the relationship of macrothrombocytopenia and TUBB1 gene. Funding: This research is financially supported by Starting R&D Projects Funding Program (3001) of The Scientific and Technological Research Council of Turkey (TUBITAK)
Session topic: E-poster
Keyword(s): Mutation analysis, Platelet polymorphism
Type: Eposter Presentation
Background
Frequency of the rare bleeding disorders (RBDs) in the general population ranges from 1:500.000 to 1:2 millions. In countries with a high rate of consanguineous marriages RBDs occur more frequently, representing a significant clinical and social problem. Macrothrombocytopenia (giant platelet syndrome) is an autosomal dominant disorder and previous studies have demonstrated that Myosin Heavy Chain 9 (MYH9) mutations lead to this disorder. The pathogenesis of almost the half of diseases related to MYH9 gene is unknown. So its diagnosis is not possible. The membrane skeleton and the link between actin filaments of skeleton and microtubules contain the normal platelet morphology. The defects occurred on these systems results with macrothrombocytopenia. The relation between macrothrombocytopenia and the defect occurred on microtubules that consisted by alpha and beta tubulin heterodimers can be explained by the defect occurred on Tubulin Beta 1 (TUBB1) gene.According to HGMD (Human Gene Mutation Database) data; 52 mutations are defined in MYH9 gene between 2004 - 2014. 17 of these mutations are defined in patients with giant thrombocyte syndrome(macrothrombocytopenia). Only 2 mutations are defined related to TUBB1 gene, so the researches done on relation between TUBB1 and macrothrombocytopenia is limited. The guiding indicators on the treatment of this disease can be achieved in case of defining the effects of TUBB1 mutations on megakaryocytes-microtubule organization, proplatelet formation and platelet morphology
Aims
In this study, we aimed to analyze TUBB1 gene at Turkish population with clinically diagnosed macrothrombocytopenia.
Methods
A written informed consent for genetic analysis was obtained from the patients. The patient blood was collected from various hematology clinics in Turkey. In this study, TUBB1 gene mutation analysis was performed by using the blood of patients diagnosed with macrothrombocytopenia following the DNA isolation. Then samples were sequenced using a DNA sequencer (Beckman Coulter, USA). Sequencing are evaluated using with FinchTV program.
Results
TUBB1 gene analysis of Turkish patients with macrothrombocytopenia revealed a novel heterozygous Cytosine to Timin nucleotide change at 821 at exon4 (p.T274M/ Threonin to Methionine), at a child and his father in the same family, 99 nucleotide ahead which is at nucleotid 920, there is a novel heterozygous Guanine to Adenin nucleotide change, this situation caused to change of Arginine aminoacid to Histidine aminoacid at 307 position (p.R307H) in protein. These changes are conserved at evolutionary process, so we can say that these transitions are novel mutations. We also identified a double base pair substitution at nucleotide positions 130-131 at exon 2,this transition encodes the Q43P (p.Gly43Pro, p.Gly43His) mutant form of the protein. (nucleotide and aminoacid numbering as per m RNA GenBank entry NM_758664)
Conclusion
In this study, we identified the first TUBB1 mutation; combined 821C>T and 920 G>A mutations in a family and these mutations are not defined previously in Human Gene Mutation Database (HGMD). And Q43P single nucleotide polymorphism is defined firstly at Turkish population, so they are very important findings in terms of explaining the relationship of macrothrombocytopenia and TUBB1 gene. Funding: This research is financially supported by Starting R&D Projects Funding Program (3001) of The Scientific and Technological Research Council of Turkey (TUBITAK)
Session topic: E-poster
Keyword(s): Mutation analysis, Platelet polymorphism
Abstract: E1423
Type: Eposter Presentation
Background
Frequency of the rare bleeding disorders (RBDs) in the general population ranges from 1:500.000 to 1:2 millions. In countries with a high rate of consanguineous marriages RBDs occur more frequently, representing a significant clinical and social problem. Macrothrombocytopenia (giant platelet syndrome) is an autosomal dominant disorder and previous studies have demonstrated that Myosin Heavy Chain 9 (MYH9) mutations lead to this disorder. The pathogenesis of almost the half of diseases related to MYH9 gene is unknown. So its diagnosis is not possible. The membrane skeleton and the link between actin filaments of skeleton and microtubules contain the normal platelet morphology. The defects occurred on these systems results with macrothrombocytopenia. The relation between macrothrombocytopenia and the defect occurred on microtubules that consisted by alpha and beta tubulin heterodimers can be explained by the defect occurred on Tubulin Beta 1 (TUBB1) gene.According to HGMD (Human Gene Mutation Database) data; 52 mutations are defined in MYH9 gene between 2004 - 2014. 17 of these mutations are defined in patients with giant thrombocyte syndrome(macrothrombocytopenia). Only 2 mutations are defined related to TUBB1 gene, so the researches done on relation between TUBB1 and macrothrombocytopenia is limited. The guiding indicators on the treatment of this disease can be achieved in case of defining the effects of TUBB1 mutations on megakaryocytes-microtubule organization, proplatelet formation and platelet morphology
Aims
In this study, we aimed to analyze TUBB1 gene at Turkish population with clinically diagnosed macrothrombocytopenia.
Methods
A written informed consent for genetic analysis was obtained from the patients. The patient blood was collected from various hematology clinics in Turkey. In this study, TUBB1 gene mutation analysis was performed by using the blood of patients diagnosed with macrothrombocytopenia following the DNA isolation. Then samples were sequenced using a DNA sequencer (Beckman Coulter, USA). Sequencing are evaluated using with FinchTV program.
Results
TUBB1 gene analysis of Turkish patients with macrothrombocytopenia revealed a novel heterozygous Cytosine to Timin nucleotide change at 821 at exon4 (p.T274M/ Threonin to Methionine), at a child and his father in the same family, 99 nucleotide ahead which is at nucleotid 920, there is a novel heterozygous Guanine to Adenin nucleotide change, this situation caused to change of Arginine aminoacid to Histidine aminoacid at 307 position (p.R307H) in protein. These changes are conserved at evolutionary process, so we can say that these transitions are novel mutations. We also identified a double base pair substitution at nucleotide positions 130-131 at exon 2,this transition encodes the Q43P (p.Gly43Pro, p.Gly43His) mutant form of the protein. (nucleotide and aminoacid numbering as per m RNA GenBank entry NM_758664)
Conclusion
In this study, we identified the first TUBB1 mutation; combined 821C>T and 920 G>A mutations in a family and these mutations are not defined previously in Human Gene Mutation Database (HGMD). And Q43P single nucleotide polymorphism is defined firstly at Turkish population, so they are very important findings in terms of explaining the relationship of macrothrombocytopenia and TUBB1 gene. Funding: This research is financially supported by Starting R&D Projects Funding Program (3001) of The Scientific and Technological Research Council of Turkey (TUBITAK)
Session topic: E-poster
Keyword(s): Mutation analysis, Platelet polymorphism
Type: Eposter Presentation
Background
Frequency of the rare bleeding disorders (RBDs) in the general population ranges from 1:500.000 to 1:2 millions. In countries with a high rate of consanguineous marriages RBDs occur more frequently, representing a significant clinical and social problem. Macrothrombocytopenia (giant platelet syndrome) is an autosomal dominant disorder and previous studies have demonstrated that Myosin Heavy Chain 9 (MYH9) mutations lead to this disorder. The pathogenesis of almost the half of diseases related to MYH9 gene is unknown. So its diagnosis is not possible. The membrane skeleton and the link between actin filaments of skeleton and microtubules contain the normal platelet morphology. The defects occurred on these systems results with macrothrombocytopenia. The relation between macrothrombocytopenia and the defect occurred on microtubules that consisted by alpha and beta tubulin heterodimers can be explained by the defect occurred on Tubulin Beta 1 (TUBB1) gene.According to HGMD (Human Gene Mutation Database) data; 52 mutations are defined in MYH9 gene between 2004 - 2014. 17 of these mutations are defined in patients with giant thrombocyte syndrome(macrothrombocytopenia). Only 2 mutations are defined related to TUBB1 gene, so the researches done on relation between TUBB1 and macrothrombocytopenia is limited. The guiding indicators on the treatment of this disease can be achieved in case of defining the effects of TUBB1 mutations on megakaryocytes-microtubule organization, proplatelet formation and platelet morphology
Aims
In this study, we aimed to analyze TUBB1 gene at Turkish population with clinically diagnosed macrothrombocytopenia.
Methods
A written informed consent for genetic analysis was obtained from the patients. The patient blood was collected from various hematology clinics in Turkey. In this study, TUBB1 gene mutation analysis was performed by using the blood of patients diagnosed with macrothrombocytopenia following the DNA isolation. Then samples were sequenced using a DNA sequencer (Beckman Coulter, USA). Sequencing are evaluated using with FinchTV program.
Results
TUBB1 gene analysis of Turkish patients with macrothrombocytopenia revealed a novel heterozygous Cytosine to Timin nucleotide change at 821 at exon4 (p.T274M/ Threonin to Methionine), at a child and his father in the same family, 99 nucleotide ahead which is at nucleotid 920, there is a novel heterozygous Guanine to Adenin nucleotide change, this situation caused to change of Arginine aminoacid to Histidine aminoacid at 307 position (p.R307H) in protein. These changes are conserved at evolutionary process, so we can say that these transitions are novel mutations. We also identified a double base pair substitution at nucleotide positions 130-131 at exon 2,this transition encodes the Q43P (p.Gly43Pro, p.Gly43His) mutant form of the protein. (nucleotide and aminoacid numbering as per m RNA GenBank entry NM_758664)
Conclusion
In this study, we identified the first TUBB1 mutation; combined 821C>T and 920 G>A mutations in a family and these mutations are not defined previously in Human Gene Mutation Database (HGMD). And Q43P single nucleotide polymorphism is defined firstly at Turkish population, so they are very important findings in terms of explaining the relationship of macrothrombocytopenia and TUBB1 gene. Funding: This research is financially supported by Starting R&D Projects Funding Program (3001) of The Scientific and Technological Research Council of Turkey (TUBITAK)
Session topic: E-poster
Keyword(s): Mutation analysis, Platelet polymorphism
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