MOLECULAR CHARACTERIZATION OF BETA GLOBIN GENE OF THALASSEMIA REVEALS NEW AND RARE MUTATIONS IN PAKISTANI POPULATION
(Abstract release date: 05/21/15)
EHA Library. Yasmeen H. 06/12/15; 102748; PB1985
Disclosure(s): University of the Punjab, Lahore PakistanDepartment of Microbiology and Molecular Genetics
Humaira Yasmeen
Contributions
Contributions
Abstract
Abstract: PB1985
Type: Publication Only
Background
Imbalance in synthesis of α- or β- chains of hemoglobin results in thalassemia that has clinically diverse manifestations ranging from asymptomatic to regularly transfusion dependent individuals. More than 200 deletions or point mutations have been identified that impair transcription, processing, or translation of α- or β-globin mRNA. In Pakistan, a carrier rate of 5 to 7 % demands communal preventive measures such as carrier identification, genetic counseling and prenatal diagnosis.
Aims
Present multicentre study undertaken in four cities of Pakistan examines the frequency and spectrum of alpha and beta thalassemia in Pakistani population.
Methods
161 seronegative beta thalassemia patients, identified on the ground of haematological parameters, were screened for mutations of the Alpha (HBA2 and HBA1) and Beta (HBB) genes and G Gamma (HBG2) Globin gene XmnI polymorphism using a combination of Multiplex Gap PCR, Sanger sequencing and RFLP PCR.
Results
Among 16 mutations identified in the beta gene, HBB:c.27_28insG (p.Ser10Val) was the most prevalent. α-3.7 and α-4.2 deletions were also found in coinheritance with beta thalassemia mutations. Rare mutations such as HBB:c.-138C>T and HBB:c.315+1G>A were also identified. Interestingly, one novel mutation (HBB:c.-148T>A), two rare variants (HBB:c.332T>C (p.Leu111Pro) and HBB:c.92G>C (p.Arg31Thr) and a novel association (HBB:c.92G>C (p.Arg31Thr)/HBB:c.-92C>G) were also reported for the first time in our study in the Pakistani population. HBG2:c.-211C>T base-pair substitution (historically described as -158 Gγ XmnI polymorphism) was present in 36% of the patients analysed.
Summary
Such comprehensive studies revealing some rare mutations are essential for prenatal screening and control of this highly prevalent disease in Pakistani population along with nationwide awareness campaign.
Keyword(s): Hemoglobin, Thalassemia
Session topic: Publication Only
Type: Publication Only
Background
Imbalance in synthesis of α- or β- chains of hemoglobin results in thalassemia that has clinically diverse manifestations ranging from asymptomatic to regularly transfusion dependent individuals. More than 200 deletions or point mutations have been identified that impair transcription, processing, or translation of α- or β-globin mRNA. In Pakistan, a carrier rate of 5 to 7 % demands communal preventive measures such as carrier identification, genetic counseling and prenatal diagnosis.
Aims
Present multicentre study undertaken in four cities of Pakistan examines the frequency and spectrum of alpha and beta thalassemia in Pakistani population.
Methods
161 seronegative beta thalassemia patients, identified on the ground of haematological parameters, were screened for mutations of the Alpha (HBA2 and HBA1) and Beta (HBB) genes and G Gamma (HBG2) Globin gene XmnI polymorphism using a combination of Multiplex Gap PCR, Sanger sequencing and RFLP PCR.
Results
Among 16 mutations identified in the beta gene, HBB:c.27_28insG (p.Ser10Val) was the most prevalent. α-3.7 and α-4.2 deletions were also found in coinheritance with beta thalassemia mutations. Rare mutations such as HBB:c.-138C>T and HBB:c.315+1G>A were also identified. Interestingly, one novel mutation (HBB:c.-148T>A), two rare variants (HBB:c.332T>C (p.Leu111Pro) and HBB:c.92G>C (p.Arg31Thr) and a novel association (HBB:c.92G>C (p.Arg31Thr)/HBB:c.-92C>G) were also reported for the first time in our study in the Pakistani population. HBG2:c.-211C>T base-pair substitution (historically described as -158 Gγ XmnI polymorphism) was present in 36% of the patients analysed.
Summary
Such comprehensive studies revealing some rare mutations are essential for prenatal screening and control of this highly prevalent disease in Pakistani population along with nationwide awareness campaign.
Keyword(s): Hemoglobin, Thalassemia
Session topic: Publication Only
Abstract: PB1985
Type: Publication Only
Background
Imbalance in synthesis of α- or β- chains of hemoglobin results in thalassemia that has clinically diverse manifestations ranging from asymptomatic to regularly transfusion dependent individuals. More than 200 deletions or point mutations have been identified that impair transcription, processing, or translation of α- or β-globin mRNA. In Pakistan, a carrier rate of 5 to 7 % demands communal preventive measures such as carrier identification, genetic counseling and prenatal diagnosis.
Aims
Present multicentre study undertaken in four cities of Pakistan examines the frequency and spectrum of alpha and beta thalassemia in Pakistani population.
Methods
161 seronegative beta thalassemia patients, identified on the ground of haematological parameters, were screened for mutations of the Alpha (HBA2 and HBA1) and Beta (HBB) genes and G Gamma (HBG2) Globin gene XmnI polymorphism using a combination of Multiplex Gap PCR, Sanger sequencing and RFLP PCR.
Results
Among 16 mutations identified in the beta gene, HBB:c.27_28insG (p.Ser10Val) was the most prevalent. α-3.7 and α-4.2 deletions were also found in coinheritance with beta thalassemia mutations. Rare mutations such as HBB:c.-138C>T and HBB:c.315+1G>A were also identified. Interestingly, one novel mutation (HBB:c.-148T>A), two rare variants (HBB:c.332T>C (p.Leu111Pro) and HBB:c.92G>C (p.Arg31Thr) and a novel association (HBB:c.92G>C (p.Arg31Thr)/HBB:c.-92C>G) were also reported for the first time in our study in the Pakistani population. HBG2:c.-211C>T base-pair substitution (historically described as -158 Gγ XmnI polymorphism) was present in 36% of the patients analysed.
Summary
Such comprehensive studies revealing some rare mutations are essential for prenatal screening and control of this highly prevalent disease in Pakistani population along with nationwide awareness campaign.
Keyword(s): Hemoglobin, Thalassemia
Session topic: Publication Only
Type: Publication Only
Background
Imbalance in synthesis of α- or β- chains of hemoglobin results in thalassemia that has clinically diverse manifestations ranging from asymptomatic to regularly transfusion dependent individuals. More than 200 deletions or point mutations have been identified that impair transcription, processing, or translation of α- or β-globin mRNA. In Pakistan, a carrier rate of 5 to 7 % demands communal preventive measures such as carrier identification, genetic counseling and prenatal diagnosis.
Aims
Present multicentre study undertaken in four cities of Pakistan examines the frequency and spectrum of alpha and beta thalassemia in Pakistani population.
Methods
161 seronegative beta thalassemia patients, identified on the ground of haematological parameters, were screened for mutations of the Alpha (HBA2 and HBA1) and Beta (HBB) genes and G Gamma (HBG2) Globin gene XmnI polymorphism using a combination of Multiplex Gap PCR, Sanger sequencing and RFLP PCR.
Results
Among 16 mutations identified in the beta gene, HBB:c.27_28insG (p.Ser10Val) was the most prevalent. α-3.7 and α-4.2 deletions were also found in coinheritance with beta thalassemia mutations. Rare mutations such as HBB:c.-138C>T and HBB:c.315+1G>A were also identified. Interestingly, one novel mutation (HBB:c.-148T>A), two rare variants (HBB:c.332T>C (p.Leu111Pro) and HBB:c.92G>C (p.Arg31Thr) and a novel association (HBB:c.92G>C (p.Arg31Thr)/HBB:c.-92C>G) were also reported for the first time in our study in the Pakistani population. HBG2:c.-211C>T base-pair substitution (historically described as -158 Gγ XmnI polymorphism) was present in 36% of the patients analysed.
Summary
Such comprehensive studies revealing some rare mutations are essential for prenatal screening and control of this highly prevalent disease in Pakistani population along with nationwide awareness campaign.
Keyword(s): Hemoglobin, Thalassemia
Session topic: Publication Only
{{ help_message }}
{{filter}}