ROLE OF GENETIC DIAGNOSIS FOR PATIENTS WITH SUSPICION OF THALASSEMIA INTERMEDIATE/MINOR
(Abstract release date: 05/19/16)
EHA Library. Babikyan D. 06/09/16; 135019; PB2119
Dr. Davit Babikyan
Contributions
Contributions
Abstract
Abstract: PB2119
Type: Publication Only
Background
Armenia is situated in the link of Mediterranean and Indo-Mediterranean belts of thalassemia. However, due to the scarcity of information restricted only for very rare reported cases it was traditionally underestimated the need of provision of genetic analysis for thalassemia associated with variable degree of anemia and hematological findings. Our previous results from population screening study suggested rather low carrier frequency however with a higher rate for alpha than for beta thalassemia.
Aims
To provide sound data about the mutation spectrum of alpha and beta globin genes in Armenia and to assess the role of genetic testing for patients with ssuspected clinical phenotype, we carried out the first genetic analysis in a cohort of Armenian patients.
Methods
All 48 sporadic and 11 familial cases of Armenian ethnicity with suspicion of mainly thalassemia intermedia or thalassemia minor had genetic testing for alpha and beta thalassemia genes who have been defined by specific hematological features, mainly by hypochromia, microcytosis, and marked variations in size and shape of the red blood cells and/or suffering from minimal anemia. Screening of 22 beta globin gene and 21 alpha globin gene mutations common for the Mediterranean and Indo-Mediterranean regions was performed using multiplex PCRs of DNA purified from blood samples of affected cases and family members. Further biotinylated amplification products were reverse-hybridized to allele-specific oligonucleotides immobilized on membrane teststrips.
Results
30 patients were diagnosed as simple heterozygotes for one of the following b0 or b+ globin gene mutations (-30 [T>A], cd8 [-AA], cd15 [TGG>TGA], cd44 [-C], IVS2.1 [G>A]) responsible for thalassemia minor or intermedia with specific hematological features. In 2 cases 3.7 alpha single gene and 20.5 alpha double gene deletion were detected, while a compound heterozygous genotype of alpha genes consisting of 20.5 alpha double gene deletion and a1 cd59 [GGC>GAC] (Hb Adana) mutation was detected in one patient. More interestingly, two patients were detected with simple heterozygous beta globin gene mutations (cd8 [-AA] or IVS1.110 [G>A]) with the co-inherited triplicated alpha globin gene rearrangement which indeed developed a clinical phenotype of intermediate beta-thalassemia.All 5 families were detected with alpha or beta globin gene mutations. Particularly, sibs in four families were detected with single b0 mutations or 20.5 alpha double gene deletion. A proband of another family had compound heterozygous genotype for beta globin mutations (cd8 [-AA] / IVS2.848 [C>A]) and parents were carriers of the beta globin mutations along with anti-3.7 alpha globin gene triplication.13 patients had no alpha globin neither beta globin gene mutations detected.
Conclusion
This is the first report of genetic screening of suspected thalassemia cases in Armenia. Despite of former pessimistic view on thalassemia in the country compared to the neighboring countries, 80% detection rate of mutations among symptomatic cases emphasizes the importance of development of genetic screening among patients with suspected phenotype with minor or intermediate thalassemia. Meanwhile, the genetic diagnosis has become possible only after having more differentiated clinical and hematological analysis. Furthermore, the screening data does not reject possibility of detection of other mutations, particularly in patients with no mutation through sequencing analysis which raises the importance of genetic testing. In contrast to the population screening data, beta thalassemia was found more frequent than alpha thalassemia. Further larger screening study is required to better understand and assess the role of mutations identified in heterozygous beta-thalassemia cases and the clinical-molecular relationships, as well as mechanisms leading to clinical and hematological severity in simple heterozygotes.
Session topic: E-poster
Keyword(s): Beta thalassemia, Genetic, Thalassemia
Type: Publication Only
Background
Armenia is situated in the link of Mediterranean and Indo-Mediterranean belts of thalassemia. However, due to the scarcity of information restricted only for very rare reported cases it was traditionally underestimated the need of provision of genetic analysis for thalassemia associated with variable degree of anemia and hematological findings. Our previous results from population screening study suggested rather low carrier frequency however with a higher rate for alpha than for beta thalassemia.
Aims
To provide sound data about the mutation spectrum of alpha and beta globin genes in Armenia and to assess the role of genetic testing for patients with ssuspected clinical phenotype, we carried out the first genetic analysis in a cohort of Armenian patients.
Methods
All 48 sporadic and 11 familial cases of Armenian ethnicity with suspicion of mainly thalassemia intermedia or thalassemia minor had genetic testing for alpha and beta thalassemia genes who have been defined by specific hematological features, mainly by hypochromia, microcytosis, and marked variations in size and shape of the red blood cells and/or suffering from minimal anemia. Screening of 22 beta globin gene and 21 alpha globin gene mutations common for the Mediterranean and Indo-Mediterranean regions was performed using multiplex PCRs of DNA purified from blood samples of affected cases and family members. Further biotinylated amplification products were reverse-hybridized to allele-specific oligonucleotides immobilized on membrane teststrips.
Results
30 patients were diagnosed as simple heterozygotes for one of the following b0 or b+ globin gene mutations (-30 [T>A], cd8 [-AA], cd15 [TGG>TGA], cd44 [-C], IVS2.1 [G>A]) responsible for thalassemia minor or intermedia with specific hematological features. In 2 cases 3.7 alpha single gene and 20.5 alpha double gene deletion were detected, while a compound heterozygous genotype of alpha genes consisting of 20.5 alpha double gene deletion and a1 cd59 [GGC>GAC] (Hb Adana) mutation was detected in one patient. More interestingly, two patients were detected with simple heterozygous beta globin gene mutations (cd8 [-AA] or IVS1.110 [G>A]) with the co-inherited triplicated alpha globin gene rearrangement which indeed developed a clinical phenotype of intermediate beta-thalassemia.All 5 families were detected with alpha or beta globin gene mutations. Particularly, sibs in four families were detected with single b0 mutations or 20.5 alpha double gene deletion. A proband of another family had compound heterozygous genotype for beta globin mutations (cd8 [-AA] / IVS2.848 [C>A]) and parents were carriers of the beta globin mutations along with anti-3.7 alpha globin gene triplication.13 patients had no alpha globin neither beta globin gene mutations detected.
Conclusion
This is the first report of genetic screening of suspected thalassemia cases in Armenia. Despite of former pessimistic view on thalassemia in the country compared to the neighboring countries, 80% detection rate of mutations among symptomatic cases emphasizes the importance of development of genetic screening among patients with suspected phenotype with minor or intermediate thalassemia. Meanwhile, the genetic diagnosis has become possible only after having more differentiated clinical and hematological analysis. Furthermore, the screening data does not reject possibility of detection of other mutations, particularly in patients with no mutation through sequencing analysis which raises the importance of genetic testing. In contrast to the population screening data, beta thalassemia was found more frequent than alpha thalassemia. Further larger screening study is required to better understand and assess the role of mutations identified in heterozygous beta-thalassemia cases and the clinical-molecular relationships, as well as mechanisms leading to clinical and hematological severity in simple heterozygotes.
Session topic: E-poster
Keyword(s): Beta thalassemia, Genetic, Thalassemia
Abstract: PB2119
Type: Publication Only
Background
Armenia is situated in the link of Mediterranean and Indo-Mediterranean belts of thalassemia. However, due to the scarcity of information restricted only for very rare reported cases it was traditionally underestimated the need of provision of genetic analysis for thalassemia associated with variable degree of anemia and hematological findings. Our previous results from population screening study suggested rather low carrier frequency however with a higher rate for alpha than for beta thalassemia.
Aims
To provide sound data about the mutation spectrum of alpha and beta globin genes in Armenia and to assess the role of genetic testing for patients with ssuspected clinical phenotype, we carried out the first genetic analysis in a cohort of Armenian patients.
Methods
All 48 sporadic and 11 familial cases of Armenian ethnicity with suspicion of mainly thalassemia intermedia or thalassemia minor had genetic testing for alpha and beta thalassemia genes who have been defined by specific hematological features, mainly by hypochromia, microcytosis, and marked variations in size and shape of the red blood cells and/or suffering from minimal anemia. Screening of 22 beta globin gene and 21 alpha globin gene mutations common for the Mediterranean and Indo-Mediterranean regions was performed using multiplex PCRs of DNA purified from blood samples of affected cases and family members. Further biotinylated amplification products were reverse-hybridized to allele-specific oligonucleotides immobilized on membrane teststrips.
Results
30 patients were diagnosed as simple heterozygotes for one of the following b0 or b+ globin gene mutations (-30 [T>A], cd8 [-AA], cd15 [TGG>TGA], cd44 [-C], IVS2.1 [G>A]) responsible for thalassemia minor or intermedia with specific hematological features. In 2 cases 3.7 alpha single gene and 20.5 alpha double gene deletion were detected, while a compound heterozygous genotype of alpha genes consisting of 20.5 alpha double gene deletion and a1 cd59 [GGC>GAC] (Hb Adana) mutation was detected in one patient. More interestingly, two patients were detected with simple heterozygous beta globin gene mutations (cd8 [-AA] or IVS1.110 [G>A]) with the co-inherited triplicated alpha globin gene rearrangement which indeed developed a clinical phenotype of intermediate beta-thalassemia.All 5 families were detected with alpha or beta globin gene mutations. Particularly, sibs in four families were detected with single b0 mutations or 20.5 alpha double gene deletion. A proband of another family had compound heterozygous genotype for beta globin mutations (cd8 [-AA] / IVS2.848 [C>A]) and parents were carriers of the beta globin mutations along with anti-3.7 alpha globin gene triplication.13 patients had no alpha globin neither beta globin gene mutations detected.
Conclusion
This is the first report of genetic screening of suspected thalassemia cases in Armenia. Despite of former pessimistic view on thalassemia in the country compared to the neighboring countries, 80% detection rate of mutations among symptomatic cases emphasizes the importance of development of genetic screening among patients with suspected phenotype with minor or intermediate thalassemia. Meanwhile, the genetic diagnosis has become possible only after having more differentiated clinical and hematological analysis. Furthermore, the screening data does not reject possibility of detection of other mutations, particularly in patients with no mutation through sequencing analysis which raises the importance of genetic testing. In contrast to the population screening data, beta thalassemia was found more frequent than alpha thalassemia. Further larger screening study is required to better understand and assess the role of mutations identified in heterozygous beta-thalassemia cases and the clinical-molecular relationships, as well as mechanisms leading to clinical and hematological severity in simple heterozygotes.
Session topic: E-poster
Keyword(s): Beta thalassemia, Genetic, Thalassemia
Type: Publication Only
Background
Armenia is situated in the link of Mediterranean and Indo-Mediterranean belts of thalassemia. However, due to the scarcity of information restricted only for very rare reported cases it was traditionally underestimated the need of provision of genetic analysis for thalassemia associated with variable degree of anemia and hematological findings. Our previous results from population screening study suggested rather low carrier frequency however with a higher rate for alpha than for beta thalassemia.
Aims
To provide sound data about the mutation spectrum of alpha and beta globin genes in Armenia and to assess the role of genetic testing for patients with ssuspected clinical phenotype, we carried out the first genetic analysis in a cohort of Armenian patients.
Methods
All 48 sporadic and 11 familial cases of Armenian ethnicity with suspicion of mainly thalassemia intermedia or thalassemia minor had genetic testing for alpha and beta thalassemia genes who have been defined by specific hematological features, mainly by hypochromia, microcytosis, and marked variations in size and shape of the red blood cells and/or suffering from minimal anemia. Screening of 22 beta globin gene and 21 alpha globin gene mutations common for the Mediterranean and Indo-Mediterranean regions was performed using multiplex PCRs of DNA purified from blood samples of affected cases and family members. Further biotinylated amplification products were reverse-hybridized to allele-specific oligonucleotides immobilized on membrane teststrips.
Results
30 patients were diagnosed as simple heterozygotes for one of the following b0 or b+ globin gene mutations (-30 [T>A], cd8 [-AA], cd15 [TGG>TGA], cd44 [-C], IVS2.1 [G>A]) responsible for thalassemia minor or intermedia with specific hematological features. In 2 cases 3.7 alpha single gene and 20.5 alpha double gene deletion were detected, while a compound heterozygous genotype of alpha genes consisting of 20.5 alpha double gene deletion and a1 cd59 [GGC>GAC] (Hb Adana) mutation was detected in one patient. More interestingly, two patients were detected with simple heterozygous beta globin gene mutations (cd8 [-AA] or IVS1.110 [G>A]) with the co-inherited triplicated alpha globin gene rearrangement which indeed developed a clinical phenotype of intermediate beta-thalassemia.All 5 families were detected with alpha or beta globin gene mutations. Particularly, sibs in four families were detected with single b0 mutations or 20.5 alpha double gene deletion. A proband of another family had compound heterozygous genotype for beta globin mutations (cd8 [-AA] / IVS2.848 [C>A]) and parents were carriers of the beta globin mutations along with anti-3.7 alpha globin gene triplication.13 patients had no alpha globin neither beta globin gene mutations detected.
Conclusion
This is the first report of genetic screening of suspected thalassemia cases in Armenia. Despite of former pessimistic view on thalassemia in the country compared to the neighboring countries, 80% detection rate of mutations among symptomatic cases emphasizes the importance of development of genetic screening among patients with suspected phenotype with minor or intermediate thalassemia. Meanwhile, the genetic diagnosis has become possible only after having more differentiated clinical and hematological analysis. Furthermore, the screening data does not reject possibility of detection of other mutations, particularly in patients with no mutation through sequencing analysis which raises the importance of genetic testing. In contrast to the population screening data, beta thalassemia was found more frequent than alpha thalassemia. Further larger screening study is required to better understand and assess the role of mutations identified in heterozygous beta-thalassemia cases and the clinical-molecular relationships, as well as mechanisms leading to clinical and hematological severity in simple heterozygotes.
Session topic: E-poster
Keyword(s): Beta thalassemia, Genetic, Thalassemia
{{ help_message }}
{{filter}}