Molecular Characterization of β- and α-Globin Gene Mutations in Individuals with Borderline Hb A2 Levels

Background: The molecular defects resulting in β-thalassemia phenotype, in the Egyptian population show a clear heterogenic mutations pattern. PCR based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of β-thalassemia is absolutely necessary for carrier screening, for genetic counseling, and to offer prenatal diagnosis.The aim of the work: was to evaluate the different β-globin gene mutations in one hundred Egyptian children with β-thalassemia. Patients and Methods: One hundred of β-thalassemic Egyptian children, covering most Egyptian Governorates. All patients were subjected to meticulous history taking, clinical examinations, complete blood count, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of β-globin gene to detect the frequency of different mutations in studied patients. Results: The most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A)19%,IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon"Cd"39(C> T) 4%,-87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (-AA), Cd29(-G), Cd5 (-CT), Cd6(-A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G> C), Cd 28 (-C), Cap+1(A>C), -88(C>A), all of these rare mutations were present in 1%. There was considerable variation in phenotypic severity among patients resulting from interaction of different β° and β+mutations, 79(79%) patients were thalassemia major (TM) and 21(21%) were thassemia intermedia (TI), without genotype phenotype association. Conclusion: Direct DNA sequencing provides insights for the frequency of different mutations in β- thalassemic patients including rare and /or unknown ones.

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Recent Advances in the Molecular Biology of Systemic Mastocytosis: Implications for Diagnosis, Prognosis, and Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms21113987 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3987 ◽

Cited By ~ 1

Author(s):

Margherita Martelli ◽

Cecilia Monaldi ◽

Sara De Santis ◽

Samantha Bruno ◽

Manuela Mancini ◽

...

Keyword(s):

Molecular Characterization ◽

Systemic Mastocytosis ◽

Gene Mutations ◽

Scoring Systems ◽

Molecular Data ◽

Loss Of Function ◽

Prognostic Information ◽

Genetic Profiling ◽

Kit D816v

In recent years, molecular characterization and management of patients with systemic mastocytosis (SM) have greatly benefited from the application of advanced technologies. Highly sensitive and accurate assays for KIT D816V mutation detection and quantification have allowed the switch to non-invasive peripheral blood testing for patient screening; allele burden has prognostic implications and may be used to monitor therapeutic efficacy. Progress in genetic profiling of KIT, together with the use of next-generation sequencing panels for the characterization of associated gene mutations, have allowed the stratification of patients into three subgroups differing in terms of pathogenesis and prognosis: (i) patients with mast cell-restricted KIT D816V; (ii) patients with multilineage KIT D816V-involvement; (iii) patients with “multi-mutated disease”. Thanks to these findings, new prognostic scoring systems combining clinical and molecular data have been developed. Finally, non-genetic SETD2 histone methyltransferase loss of function has recently been identified in advanced SM. Assessment of SETD2 protein levels and activity might provide prognostic information and has opened new research avenues exploring alternative targeted therapeutic strategies. This review discusses how progress in recent years has rapidly complemented previous knowledge improving the molecular characterization of SM, and how this has the potential to impact on patient diagnosis and management.

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Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome

Blood ◽

10.1182/blood-2003-06-1796 ◽

2003 ◽

Vol 103 (4) ◽

pp. 1305-1310 ◽

Cited By ~ 90

Author(s):

M. Matsumoto

Keyword(s):

Molecular Characterization ◽

Gene Mutations ◽

Japanese Patients

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Molecular characterization of G6PD mutations reveals the high frequency of G6PD Aures in the Lao Theung population

10.21203/rs.3.rs-45493/v4 ◽

2020 ◽

Author(s):

Amkha Sanephonasa ◽

Chalisa Louicharoen Cheepsunthorn ◽

Naly Khaminsou ◽

Onekham Savongsy ◽

Issarang Nuchprayoon ◽

...

Keyword(s):

Enzyme Activity ◽

Ethnic Group ◽

Molecular Characterization ◽

G6pd Deficiency ◽

Gene Mutations ◽

Final Diagnosis ◽

Amplification Refractory Mutation System ◽

Common Mutation ◽

Arms Pcr

Abstract Background: The prevalence and genotypes of G6PD deficiency vary worldwide, with higher prevalence in malaria endemic areas. The first time assessment of G6PD deficiency prevalence and molecular characterization of G6PD mutations in the Lao Theung population were performed in this study. Methods: A total of 252 unrelated Lao Theung participants residing in the Lao People's Democratic Republic (PDR) were recruited. All participant samples were tested for G6PD enzyme activity and G6PD gene mutations. The amplification refractory mutation system (ARMS)-PCR for detecting G6PD Aures was developed.Results: The G6PD mutations were detected in 11.51% (29/252) of the participants. Eight G6PD mutations were detected. The G6PD Aures was the most common mutation identified in this cohort, which represented 58.62 % (17/29) of all mutation. The mutation pattern was homogenous, predominantly involving the G6PD Aures mutation (6.75%), followed by 1.19% G6PD Union and 0.79% each G6PD Jammu, G6PD Mahidol and G6PD Kaiping. One subject (0.4%) each carried G6PD Viangchan and G6PD Canton. Interestingly, one case of coinheritance of G6PD Aures and Quing Yan was detected in this cohort. Based on levels of G6PD enzyme activity, the prevalence of G6PD deficiency in the Lao Theung population was 9.13 % (23/252). The prevalence of G6PD deficient males and females (activity < 30 %) in the Lao Theung population was 6.41 % (5/78) and 1.72 % (3/174), respectively, and the prevalence of G6PD intermediate (activity 30-70 %) was 5.95 % (15/252).Conclusion: The G6PD Aures mutation is highly prevalent in the Lao Theung ethnic group. The common G6PD variants in continental Southeast Asian populations, G6PD Viangchan, Canton, Kaiping, Union and Mahidol, were not prevalent in this ethnic group. The technical simplicity of the developed ARMS-PCR will facilitate the final diagnosis of the G6PD Aures.

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Molecular characterization of G6PD mutations reveals the high frequency of G6PD Aures in the Lao Theung population

10.21203/rs.3.rs-45493/v5 ◽

2021 ◽

Author(s):

Amkha Sanephonasa ◽

Chalisa Louicharoen Cheepsunthorn ◽

Naly Khaminsou ◽

Onekham Savongsy ◽

Issarang Nuchprayoon ◽

...

Keyword(s):

Enzyme Activity ◽

Ethnic Group ◽

Molecular Characterization ◽

G6pd Deficiency ◽

Gene Mutations ◽

Final Diagnosis ◽

Amplification Refractory Mutation System ◽

Common Mutation ◽

Arms Pcr

Abstract Background The prevalence and genotypes of G6PD deficiency vary worldwide, with higher prevalence in malaria endemic areas. The first-time assessment of G6PD deficiency prevalence and molecular characterization of G6PD mutations in the Lao Theung population were performed in this study. Methods A total of 252 unrelated Lao Theung participants residing in the Lao People's Democratic Republic (PDR) were recruited. All participant samples were tested for G6PD enzyme activity and G6PD gene mutations. The amplification refractory mutation system (ARMS)-PCR for detecting G6PD Aures was developed.Results The G6PD mutations were detected in 11.51% (29/252) of the participants. Eight G6PD mutations were detected. The G6PD Aures was the most common mutation identified in this cohort, which represented 58.62 % (17/29) of all mutation. The mutation pattern was homogenous, predominantly involving the G6PD Aures mutation (6.75%), followed by 1.19% G6PD Union and 0.79% each G6PD Jammu, G6PD Mahidol and G6PD Kaiping. One subject (0.4%) each carried G6PD Viangchan and G6PD Canton. Interestingly, one case of coinheritance of G6PD Aures and Quing Yan was detected in this cohort. Based on levels of G6PD enzyme activity, the prevalence of G6PD deficiency in the Lao Theung population was 9.13 % (23/252). The prevalence of G6PD deficient males and females (activity < 30 %) in the Lao Theung population was 6.41 % (5/78) and 1.72 % (3/174), respectively, and the prevalence of G6PD intermediate (activity 30-70 %) was 5.95 % (15/252).Conclusion The G6PD Aures mutation is highly prevalent in the Lao Theung ethnic group. The common G6PD variants in continental Southeast Asian populations, G6PD Viangchan, Canton, Kaiping, Union and Mahidol, were not prevalent in this ethnic group. The technical simplicity of the developed ARMS-PCR will facilitate the final diagnosis of the G6PD Aures.

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Molecular Characterization of Proprotein Convertase Subtilisin/Kexin Type 9 Gene Mutations in Vietnamese Patients with Hypercholesterolemia

Pharmacophore ◽

10.51847/w5tounb2bw ◽

2021 ◽

Vol 12 (3) ◽

pp. 23-28

Author(s):

Phuong Dong Tran Nguyen ◽

Nang Hoang Pham ◽

Phuong Kim Truong

Keyword(s):

Molecular Characterization ◽

Gene Mutations ◽

Proprotein Convertase

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Molecular characterization of 22 novel UDP-N-acetylglucosamine-1-phosphate transferase α- and β-subunit (GNPTAB) gene mutations causing mucolipidosis types IIα/β and IIIα/β in 46 patients

Human Mutation ◽

10.1002/humu.21099 ◽

2009 ◽

Vol 30 (11) ◽

pp. E956-E973 ◽

Cited By ~ 31

Author(s):

Barbara Tappino ◽

Nadia A. Chuzhanova ◽

Stefano Regis ◽

Andrea Dardis ◽

Fabio Corsolini ◽

...

Keyword(s):

Molecular Characterization ◽

Gene Mutations ◽

Β Subunit

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Genotype-phenotype correlation of HbH disease in northern Iraq

BMC Medical Genetics ◽

10.1186/s12881-020-01141-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Rawand P. Shamoon ◽

Ahmed K. Yassin ◽

Ranan K. Polus ◽

Mohamad D. Ali

Keyword(s):

Globin Gene ◽

Gene Mutations ◽

Globin Genes ◽

Phenotype Correlation ◽

Deletion Mutations ◽

Northern Iraq ◽

Screening And Prevention ◽

First Time ◽

Hbh Disease

Abstract Background HbH disease results from dysfunction of three, less commonly two, α-globin genes through various combinations of deletion and non-deletion mutations. Characterization of the mutations and the underlying genotypes is fundamental for proper screening and prevention of thalassaemia in any region. The aim of this study was to explore the genetic arrangements of HbH disease and to correlate the genotypes with the clinical phenotypes. Methods A total of 44 HbH disease patients were enrolled in this study. They were clinically and haematologically assessed. The patients were tested for 21 common α-globin gene mutations using multiplex PCR and reverse hybridization. According to the genotype, the patients were categorized into two separate sub-groups, deletion and non-deletion types HbH disease. Results Within the studied HbH disease patients, eight different α-globin gene mutations were detected in nine different genetic arrangements. The --MED and -α3.7 deletions were the two most frequently encountered mutations (37.5 and 35.2% respectively). Patients with deletion genotypes constituted 70.4%. The most common detected genotype was --MED/−α3.7 (59.1%), followed by αpoly-A1α/αpoly-A1α (13.6%). For the first time, coinheritance of two relatively mild mutations (−α3.7/ααAdana) was unpredictably detected in a 1.5 year-old child with Hb of 7.1 g/dL. Conclusion The HbH disease patients’ clinical characteristics were variable with no ample difference between the deletion and non-deletion types. These results can be of benefit for the screening and management of thalassaemia in this region.

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