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A Srivastava - One of the best experts on this subject based on the ideXlab platform.
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molecular genetics of hereditary Prothrombin Deficiency in indian patients identification of a novel ala362 thr Prothrombin vellore 1 mutation
Journal of Thrombosis and Haemostasis, 2005Co-Authors: Giridhara R Jayandharan, Auro Viswabandya, Shoma Baidya, S C Nair, R V Shaji, Mammen Chandy, A SrivastavaAbstract:Summary. Prothrombin Deficiency is a rare (1:200 000) autosomal recessive disorder caused by diverse mutations in Prothrombin gene. We have studied the molecular basis of this disorder in four unrelated Indian patients. The diagnosis was based on prolonged Prothrombin (PT) and activated partial thromboplastin times and low factor II coagulant activity (FII: C) measured using a PT based assay. FII: C levels ranged between 4.7% and 17.5%. Mutations were identified in all the four patients. Five different causative mutations including four (80%) missense and an in-frame deletion (20%) were identified. One of them was a novel, Ala362Thr aminoacid change affecting ‘B’ chain of α-thrombin. This mutation was present in a compound heterozygous state with a previously reported Arg-1Gln missense change affecting pro-peptide cleavage site. Ala362Thr occurred at a codon, evolutionarily conserved in all the 24 different Prothrombins or its related serine proteases studied. Molecular modeling of this mutation was found to cause a conformational change around the region involving a catalytic triad residue His363 and a cysteine residue at codon 364. The FII: C level in this patient was 17.5%. Three other previously reported mutations were also detected in the homozygous state: Arg271Cys in Kringle-2 region, a Glu309Lys in ‘A’ chain of α-thrombin and an in-frame deletion of 3 bp (AAG) leading to Del Lys301/302 in ‘A’ chain of α-thrombin. This is the first report of the molecular basis of Prothrombin Deficiency in Indian patients and we suggest the eponym ‘Prothrombin Vellore 1’ for Ala362Thr mutation.
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molecular genetics of hereditary Prothrombin Deficiency in indian patients identification of a novel ala362 thr Prothrombin vellore 1 mutation by conformation sensitive gel electrophoresis
Blood, 2004Co-Authors: Giridhara R Jayandharan, S C Nair, R V Shaji, Mammen Chandy, Auro Viswabandhya, Joy John Mammen, Biju George, Vikram Mathews, A SrivastavaAbstract:Prothrombin Deficiency is a rare (1:200000) autosomal recessive disorder caused by diverse mutations in Prothrombin gene. We have studied the molecular basis of this disorder in 4 unrelated Indian patients. The clinical features of these patients included easy bruisability, post-traumatic bleeds, hemarthroses (50% each) and epistaxis, gum bleedings, menorrhagia, hematemesis and post-surgical bleeding (25% each). The diagnosis was based on prolonged Prothrombin and activated partial thromboplastin times and low factor II coagulant activity (FII: C) measured using a Prothrombin time based assay. FII: C levels ranged between 4.7–17.5%. Genomic DNA was screened for Prothrombin gene mutations by a novel PCR and conformation sensitive gel electrophoresis (CSGE) strategy. Fourteen exonic and their flanking intronic regions and 3′ untranslated region of Prothrombin gene were amplified by 12 pairs of primers designed by Primer3 software. CSGE was performed in a mildly denaturing gel containing 10% acrylamide. Samples displaying abnormal CSGE profiles were sequenced by the Big Dye Terminator cycle sequencing kit to confirm the nature of nucleotide change. A novel missense mutation was studied based on the coordinates (identifier 1ppb) for the human ∞-thrombin (1.92A resolution) three-dimensional structure. The evolutionary conservation of this aminoacid, mutated by missense change, was studied in the Prothrombin sequence in 17 different species and 7 related proteases obtained from SwissProt and Trembl databases using PSI-BLAST. Mutations were identified in all the four patients. Five different causative mutations including 4 (80%) missense and an in-frame deletion (20%) were identified. One of them was a novel, Ala362→Thr aminoacid change affecting ‘B’ chain of ∞-thrombin. This mutation was identified in a compound heterozygous state with a previously reported Arg-1→Gln missense change affecting pro-peptide cleavage site. Ala362→Thr occurred at a codon, evolutionarily conserved in all the 24 different Prothrombins or its related serine proteases studied. This indicates its importance to the structure of α-thrombin. Molecular modeling of this Ala362→Thr mutation was found to cause a conformational change around the region involving a catalytic triad residue His363 and a cysteine residue at codon 364 due to the accommodation of a larger and polar side chain of threonine. The FII: C level in this patient was 17.5%. Three other previously reported mutations were also detected in the homozygous state: Arg271→Cys missense mutation in Kringle-2 region, a Glu309→Lys missense mutation in ‘A’ chain of ∞-thrombin and an in-frame deletion of 3bp (AAG) leading to Del Lys301/302 in ‘A’ chain of ∞-thrombin. This is the first report of the molecular basis of Prothrombin Deficiency in Indian patients and we suggest the eponym ‘Prothrombin Vellore 1′ for Ala362→Thr mutation.
Howard A. Liebman - One of the best experts on this subject based on the ideXlab platform.
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a fatal bleeding disorder due to antibody mediated acquired factor x and Prothrombin Deficiency
Blood, 2006Co-Authors: Leanne Rochanda, Gregory J Del Zoppo, Donald I. Feinstein, Howard A. LiebmanAbstract:Abnormalities in hemostasis are well described in patients with malignant disorders. While hemostatic activation resulting in thrombosis is most often described, acquired hemorrhagic disorders have also been reported. We report a case of a fatal hemorrhagic disorder in a lymphoma patient due to an acquired Factor X and Prothrombin Deficiency. The patient’s plasma contained a non-inhibitory IgG antibody that cross-reacted with and cleared from the circulation both Factor X and Prothrombin. The patient was a 72 year old male who was first noted to have persistant bleeding after angioplasty in 1991. Over the subsequent 10 years he had repeated bleeding episodes and was noted to have a prolonged PT and a PTT which corrected with a 50–50 mix of normal plasma. In 2002 he was diagnosed with a monocytooid B cell lymphoma. In April 2002 the patient had an extensive hemostatic evaluation by one of the authors (DIF) which is included in Table 1. These studies again showed a prolonged PT and aPTT which corrected with a 50–50 mix. Factor II activity and antigen were significantly reduced. While Factor X activity was low normal, Factor X antigen was decreased compared to the normal controls. Patient IgG was then isolated by Stap A chromatography and anit-Prothrombin antibodies directed were isolated by affinity chromatography on Prothrombin-sepharose. Isolated antibodies were subtyped as an IgG subclass 4. The antibodies were assayed for their interaction with Prothrombin by a direct binding ELISA and found to be calcium dependent since they did not bind in the presence of 5 mM EDTA. The interaction of the affinity isolated antibody with Prothrombin, Factor X and Factor IX was assessed using the Western Blot method. Surprisingly, the antibody also bound strongly to Factor X and to a lesser degree to Factor IX. Western blot analysis of the Factor X and Factor IX preparations using a monoclonal anti-Prothrombin antibody failed to demonstrate any Prothrombin contamination of these proteins. A competition ELISA using Prothrombin, Factor X and Factor IX showed that the antibody had a 3-fold greater affinity to Factor X then Prothrombin. A Western blot using purified Prothrombin fragment F1.2 confirmed that the antibody bound to a metal dependent conformational determinant on the amino-terminal Gla containing region of Factor II. In April 2003 the patient developed weakness in his left leg and was found to have a right parietotemporal subdural hematoma. Factor II activity was again only 34%. Intravenous IgG 1gm/kg on two separate days did not correct his coagulation studies. In June 2003 the patient developed a new large left sudural hematoma. He rapidly deteriorated and expired. We previosuly reported a lymphoma patient who developed acquired Prothrombin Deficiency associated with a non-inhibitory antibody (Cancer2001; 91: 636), however, this is the first reported case of combined acquired Factor X and Prothrombin Deficiency due to a cross-reactive non-inhibitory IgG antibody.
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a fatal bleeding disorder due to antibody mediated acquired factor x and Prothrombin Deficiency
Blood, 2006Co-Authors: Leanne Rochanda, Gregory J Del Zoppo, Donald I. Feinstein, Howard A. LiebmanAbstract:Abnormalities in hemostasis are well described in patients with malignant disorders. While hemostatic activation resulting in thrombosis is most often described, acquired hemorrhagic disorders have also been reported. We report a case of a fatal hemorrhagic disorder in a lymphoma patient due to an acquired Factor X and Prothrombin Deficiency. The patient’s plasma contained a non-inhibitory IgG antibody that cross-reacted with and cleared from the circulation both Factor X and Prothrombin. The patient was a 72 year old male who was first noted to have persistant bleeding after angioplasty in 1991. Over the subsequent 10 years he had repeated bleeding episodes and was noted to have a prolonged PT and a PTT which corrected with a 50–50 mix of normal plasma. In 2002 he was diagnosed with a monocytooid B cell lymphoma. In April 2002 the patient had an extensive hemostatic evaluation by one of the authors (DIF) which is included in Table 1. These studies again showed a prolonged PT and aPTT which corrected with a 50–50 mix. Factor II activity and antigen were significantly reduced. While Factor X activity was low normal, Factor X antigen was decreased compared to the normal controls. Patient IgG was then isolated by Stap A chromatography and anit-Prothrombin antibodies directed were isolated by affinity chromatography on Prothrombin-sepharose. Isolated antibodies were subtyped as an IgG subclass 4. The antibodies were assayed for their interaction with Prothrombin by a direct binding ELISA and found to be calcium dependent since they did not bind in the presence of 5 mM EDTA. The interaction of the affinity isolated antibody with Prothrombin, Factor X and Factor IX was assessed using the Western Blot method. Surprisingly, the antibody also bound strongly to Factor X and to a lesser degree to Factor IX. Western blot analysis of the Factor X and Factor IX preparations using a monoclonal anti-Prothrombin antibody failed to demonstrate any Prothrombin contamination of these proteins. A competition ELISA using Prothrombin, Factor X and Factor IX showed that the antibody had a 3-fold greater affinity to Factor X then Prothrombin. A Western blot using purified Prothrombin fragment F1.2 confirmed that the antibody bound to a metal dependent conformational determinant on the amino-terminal Gla containing region of Factor II. In April 2003 the patient developed weakness in his left leg and was found to have a right parietotemporal subdural hematoma. Factor II activity was again only 34%. Intravenous IgG 1gm/kg on two separate days did not correct his coagulation studies. In June 2003 the patient developed a new large left sudural hematoma. He rapidly deteriorated and expired. We previosuly reported a lymphoma patient who developed acquired Prothrombin Deficiency associated with a non-inhibitory antibody (Cancer2001; 91: 636), however, this is the first reported case of combined acquired Factor X and Prothrombin Deficiency due to a cross-reactive non-inhibitory IgG antibody.
Giridhara R Jayandharan - One of the best experts on this subject based on the ideXlab platform.
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molecular genetics of hereditary Prothrombin Deficiency in indian patients identification of a novel ala362 thr Prothrombin vellore 1 mutation
Journal of Thrombosis and Haemostasis, 2005Co-Authors: Giridhara R Jayandharan, Auro Viswabandya, Shoma Baidya, S C Nair, R V Shaji, Mammen Chandy, A SrivastavaAbstract:Summary. Prothrombin Deficiency is a rare (1:200 000) autosomal recessive disorder caused by diverse mutations in Prothrombin gene. We have studied the molecular basis of this disorder in four unrelated Indian patients. The diagnosis was based on prolonged Prothrombin (PT) and activated partial thromboplastin times and low factor II coagulant activity (FII: C) measured using a PT based assay. FII: C levels ranged between 4.7% and 17.5%. Mutations were identified in all the four patients. Five different causative mutations including four (80%) missense and an in-frame deletion (20%) were identified. One of them was a novel, Ala362Thr aminoacid change affecting ‘B’ chain of α-thrombin. This mutation was present in a compound heterozygous state with a previously reported Arg-1Gln missense change affecting pro-peptide cleavage site. Ala362Thr occurred at a codon, evolutionarily conserved in all the 24 different Prothrombins or its related serine proteases studied. Molecular modeling of this mutation was found to cause a conformational change around the region involving a catalytic triad residue His363 and a cysteine residue at codon 364. The FII: C level in this patient was 17.5%. Three other previously reported mutations were also detected in the homozygous state: Arg271Cys in Kringle-2 region, a Glu309Lys in ‘A’ chain of α-thrombin and an in-frame deletion of 3 bp (AAG) leading to Del Lys301/302 in ‘A’ chain of α-thrombin. This is the first report of the molecular basis of Prothrombin Deficiency in Indian patients and we suggest the eponym ‘Prothrombin Vellore 1’ for Ala362Thr mutation.
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molecular genetics of hereditary Prothrombin Deficiency in indian patients identification of a novel ala362 thr Prothrombin vellore 1 mutation by conformation sensitive gel electrophoresis
Blood, 2004Co-Authors: Giridhara R Jayandharan, S C Nair, R V Shaji, Mammen Chandy, Auro Viswabandhya, Joy John Mammen, Biju George, Vikram Mathews, A SrivastavaAbstract:Prothrombin Deficiency is a rare (1:200000) autosomal recessive disorder caused by diverse mutations in Prothrombin gene. We have studied the molecular basis of this disorder in 4 unrelated Indian patients. The clinical features of these patients included easy bruisability, post-traumatic bleeds, hemarthroses (50% each) and epistaxis, gum bleedings, menorrhagia, hematemesis and post-surgical bleeding (25% each). The diagnosis was based on prolonged Prothrombin and activated partial thromboplastin times and low factor II coagulant activity (FII: C) measured using a Prothrombin time based assay. FII: C levels ranged between 4.7–17.5%. Genomic DNA was screened for Prothrombin gene mutations by a novel PCR and conformation sensitive gel electrophoresis (CSGE) strategy. Fourteen exonic and their flanking intronic regions and 3′ untranslated region of Prothrombin gene were amplified by 12 pairs of primers designed by Primer3 software. CSGE was performed in a mildly denaturing gel containing 10% acrylamide. Samples displaying abnormal CSGE profiles were sequenced by the Big Dye Terminator cycle sequencing kit to confirm the nature of nucleotide change. A novel missense mutation was studied based on the coordinates (identifier 1ppb) for the human ∞-thrombin (1.92A resolution) three-dimensional structure. The evolutionary conservation of this aminoacid, mutated by missense change, was studied in the Prothrombin sequence in 17 different species and 7 related proteases obtained from SwissProt and Trembl databases using PSI-BLAST. Mutations were identified in all the four patients. Five different causative mutations including 4 (80%) missense and an in-frame deletion (20%) were identified. One of them was a novel, Ala362→Thr aminoacid change affecting ‘B’ chain of ∞-thrombin. This mutation was identified in a compound heterozygous state with a previously reported Arg-1→Gln missense change affecting pro-peptide cleavage site. Ala362→Thr occurred at a codon, evolutionarily conserved in all the 24 different Prothrombins or its related serine proteases studied. This indicates its importance to the structure of α-thrombin. Molecular modeling of this Ala362→Thr mutation was found to cause a conformational change around the region involving a catalytic triad residue His363 and a cysteine residue at codon 364 due to the accommodation of a larger and polar side chain of threonine. The FII: C level in this patient was 17.5%. Three other previously reported mutations were also detected in the homozygous state: Arg271→Cys missense mutation in Kringle-2 region, a Glu309→Lys missense mutation in ‘A’ chain of ∞-thrombin and an in-frame deletion of 3bp (AAG) leading to Del Lys301/302 in ‘A’ chain of ∞-thrombin. This is the first report of the molecular basis of Prothrombin Deficiency in Indian patients and we suggest the eponym ‘Prothrombin Vellore 1′ for Ala362→Thr mutation.
R V Shaji - One of the best experts on this subject based on the ideXlab platform.
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molecular genetics of hereditary Prothrombin Deficiency in indian patients identification of a novel ala362 thr Prothrombin vellore 1 mutation
Journal of Thrombosis and Haemostasis, 2005Co-Authors: Giridhara R Jayandharan, Auro Viswabandya, Shoma Baidya, S C Nair, R V Shaji, Mammen Chandy, A SrivastavaAbstract:Summary. Prothrombin Deficiency is a rare (1:200 000) autosomal recessive disorder caused by diverse mutations in Prothrombin gene. We have studied the molecular basis of this disorder in four unrelated Indian patients. The diagnosis was based on prolonged Prothrombin (PT) and activated partial thromboplastin times and low factor II coagulant activity (FII: C) measured using a PT based assay. FII: C levels ranged between 4.7% and 17.5%. Mutations were identified in all the four patients. Five different causative mutations including four (80%) missense and an in-frame deletion (20%) were identified. One of them was a novel, Ala362Thr aminoacid change affecting ‘B’ chain of α-thrombin. This mutation was present in a compound heterozygous state with a previously reported Arg-1Gln missense change affecting pro-peptide cleavage site. Ala362Thr occurred at a codon, evolutionarily conserved in all the 24 different Prothrombins or its related serine proteases studied. Molecular modeling of this mutation was found to cause a conformational change around the region involving a catalytic triad residue His363 and a cysteine residue at codon 364. The FII: C level in this patient was 17.5%. Three other previously reported mutations were also detected in the homozygous state: Arg271Cys in Kringle-2 region, a Glu309Lys in ‘A’ chain of α-thrombin and an in-frame deletion of 3 bp (AAG) leading to Del Lys301/302 in ‘A’ chain of α-thrombin. This is the first report of the molecular basis of Prothrombin Deficiency in Indian patients and we suggest the eponym ‘Prothrombin Vellore 1’ for Ala362Thr mutation.
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molecular genetics of hereditary Prothrombin Deficiency in indian patients identification of a novel ala362 thr Prothrombin vellore 1 mutation by conformation sensitive gel electrophoresis
Blood, 2004Co-Authors: Giridhara R Jayandharan, S C Nair, R V Shaji, Mammen Chandy, Auro Viswabandhya, Joy John Mammen, Biju George, Vikram Mathews, A SrivastavaAbstract:Prothrombin Deficiency is a rare (1:200000) autosomal recessive disorder caused by diverse mutations in Prothrombin gene. We have studied the molecular basis of this disorder in 4 unrelated Indian patients. The clinical features of these patients included easy bruisability, post-traumatic bleeds, hemarthroses (50% each) and epistaxis, gum bleedings, menorrhagia, hematemesis and post-surgical bleeding (25% each). The diagnosis was based on prolonged Prothrombin and activated partial thromboplastin times and low factor II coagulant activity (FII: C) measured using a Prothrombin time based assay. FII: C levels ranged between 4.7–17.5%. Genomic DNA was screened for Prothrombin gene mutations by a novel PCR and conformation sensitive gel electrophoresis (CSGE) strategy. Fourteen exonic and their flanking intronic regions and 3′ untranslated region of Prothrombin gene were amplified by 12 pairs of primers designed by Primer3 software. CSGE was performed in a mildly denaturing gel containing 10% acrylamide. Samples displaying abnormal CSGE profiles were sequenced by the Big Dye Terminator cycle sequencing kit to confirm the nature of nucleotide change. A novel missense mutation was studied based on the coordinates (identifier 1ppb) for the human ∞-thrombin (1.92A resolution) three-dimensional structure. The evolutionary conservation of this aminoacid, mutated by missense change, was studied in the Prothrombin sequence in 17 different species and 7 related proteases obtained from SwissProt and Trembl databases using PSI-BLAST. Mutations were identified in all the four patients. Five different causative mutations including 4 (80%) missense and an in-frame deletion (20%) were identified. One of them was a novel, Ala362→Thr aminoacid change affecting ‘B’ chain of ∞-thrombin. This mutation was identified in a compound heterozygous state with a previously reported Arg-1→Gln missense change affecting pro-peptide cleavage site. Ala362→Thr occurred at a codon, evolutionarily conserved in all the 24 different Prothrombins or its related serine proteases studied. This indicates its importance to the structure of α-thrombin. Molecular modeling of this Ala362→Thr mutation was found to cause a conformational change around the region involving a catalytic triad residue His363 and a cysteine residue at codon 364 due to the accommodation of a larger and polar side chain of threonine. The FII: C level in this patient was 17.5%. Three other previously reported mutations were also detected in the homozygous state: Arg271→Cys missense mutation in Kringle-2 region, a Glu309→Lys missense mutation in ‘A’ chain of ∞-thrombin and an in-frame deletion of 3bp (AAG) leading to Del Lys301/302 in ‘A’ chain of ∞-thrombin. This is the first report of the molecular basis of Prothrombin Deficiency in Indian patients and we suggest the eponym ‘Prothrombin Vellore 1′ for Ala362→Thr mutation.
S C Nair - One of the best experts on this subject based on the ideXlab platform.
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molecular genetics of hereditary Prothrombin Deficiency in indian patients identification of a novel ala362 thr Prothrombin vellore 1 mutation
Journal of Thrombosis and Haemostasis, 2005Co-Authors: Giridhara R Jayandharan, Auro Viswabandya, Shoma Baidya, S C Nair, R V Shaji, Mammen Chandy, A SrivastavaAbstract:Summary. Prothrombin Deficiency is a rare (1:200 000) autosomal recessive disorder caused by diverse mutations in Prothrombin gene. We have studied the molecular basis of this disorder in four unrelated Indian patients. The diagnosis was based on prolonged Prothrombin (PT) and activated partial thromboplastin times and low factor II coagulant activity (FII: C) measured using a PT based assay. FII: C levels ranged between 4.7% and 17.5%. Mutations were identified in all the four patients. Five different causative mutations including four (80%) missense and an in-frame deletion (20%) were identified. One of them was a novel, Ala362Thr aminoacid change affecting ‘B’ chain of α-thrombin. This mutation was present in a compound heterozygous state with a previously reported Arg-1Gln missense change affecting pro-peptide cleavage site. Ala362Thr occurred at a codon, evolutionarily conserved in all the 24 different Prothrombins or its related serine proteases studied. Molecular modeling of this mutation was found to cause a conformational change around the region involving a catalytic triad residue His363 and a cysteine residue at codon 364. The FII: C level in this patient was 17.5%. Three other previously reported mutations were also detected in the homozygous state: Arg271Cys in Kringle-2 region, a Glu309Lys in ‘A’ chain of α-thrombin and an in-frame deletion of 3 bp (AAG) leading to Del Lys301/302 in ‘A’ chain of α-thrombin. This is the first report of the molecular basis of Prothrombin Deficiency in Indian patients and we suggest the eponym ‘Prothrombin Vellore 1’ for Ala362Thr mutation.
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molecular genetics of hereditary Prothrombin Deficiency in indian patients identification of a novel ala362 thr Prothrombin vellore 1 mutation by conformation sensitive gel electrophoresis
Blood, 2004Co-Authors: Giridhara R Jayandharan, S C Nair, R V Shaji, Mammen Chandy, Auro Viswabandhya, Joy John Mammen, Biju George, Vikram Mathews, A SrivastavaAbstract:Prothrombin Deficiency is a rare (1:200000) autosomal recessive disorder caused by diverse mutations in Prothrombin gene. We have studied the molecular basis of this disorder in 4 unrelated Indian patients. The clinical features of these patients included easy bruisability, post-traumatic bleeds, hemarthroses (50% each) and epistaxis, gum bleedings, menorrhagia, hematemesis and post-surgical bleeding (25% each). The diagnosis was based on prolonged Prothrombin and activated partial thromboplastin times and low factor II coagulant activity (FII: C) measured using a Prothrombin time based assay. FII: C levels ranged between 4.7–17.5%. Genomic DNA was screened for Prothrombin gene mutations by a novel PCR and conformation sensitive gel electrophoresis (CSGE) strategy. Fourteen exonic and their flanking intronic regions and 3′ untranslated region of Prothrombin gene were amplified by 12 pairs of primers designed by Primer3 software. CSGE was performed in a mildly denaturing gel containing 10% acrylamide. Samples displaying abnormal CSGE profiles were sequenced by the Big Dye Terminator cycle sequencing kit to confirm the nature of nucleotide change. A novel missense mutation was studied based on the coordinates (identifier 1ppb) for the human ∞-thrombin (1.92A resolution) three-dimensional structure. The evolutionary conservation of this aminoacid, mutated by missense change, was studied in the Prothrombin sequence in 17 different species and 7 related proteases obtained from SwissProt and Trembl databases using PSI-BLAST. Mutations were identified in all the four patients. Five different causative mutations including 4 (80%) missense and an in-frame deletion (20%) were identified. One of them was a novel, Ala362→Thr aminoacid change affecting ‘B’ chain of ∞-thrombin. This mutation was identified in a compound heterozygous state with a previously reported Arg-1→Gln missense change affecting pro-peptide cleavage site. Ala362→Thr occurred at a codon, evolutionarily conserved in all the 24 different Prothrombins or its related serine proteases studied. This indicates its importance to the structure of α-thrombin. Molecular modeling of this Ala362→Thr mutation was found to cause a conformational change around the region involving a catalytic triad residue His363 and a cysteine residue at codon 364 due to the accommodation of a larger and polar side chain of threonine. The FII: C level in this patient was 17.5%. Three other previously reported mutations were also detected in the homozygous state: Arg271→Cys missense mutation in Kringle-2 region, a Glu309→Lys missense mutation in ‘A’ chain of ∞-thrombin and an in-frame deletion of 3bp (AAG) leading to Del Lys301/302 in ‘A’ chain of ∞-thrombin. This is the first report of the molecular basis of Prothrombin Deficiency in Indian patients and we suggest the eponym ‘Prothrombin Vellore 1′ for Ala362→Thr mutation.
