title: Beta thalassemia in 31,734 cases with HBB gene mutations: Pathogenic and structural analysis of the common mutations; Iran as the crossroads of the Middle East.
abstract: Thalassemia is one of the most common single gene disorders worldwide. Nearly 80 to 90 million with minor beta thalassemia and 60-70 thousand affected infants are born annually worldwide. A comprehensive search on several databases including PubMed, InterScience, British Library Direct, and Science Direct was performed extracting papers about mutation detection and frequency of beta thalassemia. All papers reporting on the mutation frequency of beta thalassemia patients were selected to analyze the frequency of mutations in different regions and various ethnicities. Mutations of 31,734 individuals were identified. Twenty common mutations were selected for further analysis. Genotype-phenotype correlation, interactome, and in silico analyses of the mutations were performed using available bioinformatics tools. Secondary structure prediction was achieved for two common mutations with online tools. The mutations were also common among the countries neighboring Iran, which are responsible for 71% to 98% of mutations. Computational analyses could be used in addition to segregation and expression analysis to assess the extent of pathogenicity of the variant. The genetics of beta thalassemia in Iran is more extensively heterogeneous than in neighboring countries. Some common mutations have arisen historically from Iran and moved to other populations due to population migrations. Also, due to genetic drift, the frequencies of some mutations have increased in small populations.
authors.affiliation: Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Nejat
authors.initials: N
authors.lastname: Mahdieh
authors.affiliation: Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran; Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: baharehrabbani@yahoo.com.
authors.forename: Bahareh
authors.initials: B
authors.lastname: Rabbani
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008877:Middle East / Q000453:epidemiology; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D013329:Structure-Activity Relationship; D055544:beta-Globins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D055544:beta-Globins
keywords: Beta-thalassemia; HBB mutations; In silico analysis