A Comprehensive Review of Gene Mutations in Inherited Blood Disorders Among the Saudi Population.
PMID 41929524 | PMCID PMC13042357 | DOI 10.1155/humu/2418005 · Human mutation · 2026
BACKGROUND: Inherited blood disorders (IBDs) are a major health concern in the Kingdom of Saudi Arabia (KSA), largely due to the high prevalence of consanguineous marriages. OBJECTIVES: This review is aimed at summarizing gene mutations and variants associated with IBDs in the Saudi population to enhance diagnosis and personalized care. METHODS: Published studies on IBD-related genetic mutations in Saudis were systematically retrieved from PubMed, Web of Science, Google Scholar, and EGEMS database using keywords "gene," "Saudi," "polymorphism," and "the different inherited blood disorders." A total of 118 studies published between 2015 and 2024 met the inclusion criteria. RESULTS: The β-globin (HBB) gene showed the greatest mutational diversity, with over 60 β-thalassemia variants identified. The α-globin genes (HBA1, HBA2, and the unique HBA12) were frequently involved in α-thalassemia, with the -α3.7 deletion predominating. In sickle cell disease, the HbS mutation (c.20A>T) is the most common, primarily linked to the Arab-Indian haplotype, whereas polymorphisms in BCL11A, HBS1L-MYB, and ANTXR1 influenced fetal hemoglobin levels. Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13. Rare disorders such as Wiskott-Aldrich syndrome (WAS) and coagulation factor deficiencies (e.g., FX, F7, and F8) were also reported. CONCLUSION: The Saudi population exhibits a distinct and diverse spectrum of IBD-related mutations. Understanding these genetic patterns can enhance diagnostic precision, guide genetic counseling, and advance personalized medicine initiatives across the Kingdom.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | HBB | “RESULTS: The β-globin (HBB) gene showed the greatest mutational diversity, with over 60 β-thalassemia variants identified.” | 0.98 | hgnc_dict_v1 |
| gene | HBA1 | “The α-globin genes (HBA1, HBA2, and the unique HBA12) were frequently involved in α-thalassemia, with the -α3.7 deletion predominating.” | 0.98 | hgnc_dict_v1 |
| gene | HBA2 | “The α-globin genes (HBA1, HBA2, and the unique HBA12) were frequently involved in α-thalassemia, with the -α3.7 deletion predominating.” | 0.98 | hgnc_dict_v1 |
| gene | BCL11A | “In sickle cell disease, the HbS mutation (c.20A>T) is the most common, primarily linked to the Arab-Indian haplotype, whereas polymorphisms in BCL11A, HBS1L-MYB, and ANTXR1 influenced fetal hemoglobin levels.” | 0.98 | hgnc_dict_v1 |
| gene | ANTXR1 | “In sickle cell disease, the HbS mutation (c.20A>T) is the most common, primarily linked to the Arab-Indian haplotype, whereas polymorphisms in BCL11A, HBS1L-MYB, and ANTXR1 influenced fetal hemoglobin levels.” | 0.98 | hgnc_dict_v1 |
| gene | F5 | “Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13.” | 0.98 | hgnc_dict_v1 |
| gene | SERPINC1 | “Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13.” | 0.98 | hgnc_dict_v1 |
| gene | MTHFR | “Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13.” | 0.98 | hgnc_dict_v1 |
| gene | MPL | “Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13.” | 0.98 | hgnc_dict_v1 |
| gene | ANKRD26 | “Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13.” | 0.98 | hgnc_dict_v1 |
| gene | THPO | “Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13.” | 0.98 | hgnc_dict_v1 |
| gene | DIAPH1 | “Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13.” | 0.98 | hgnc_dict_v1 |
| gene | ADAMTS13 | “Frequent thrombophilia-related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13.” | 0.98 | hgnc_dict_v1 |
| phenotype | sickle cell disease | “In sickle cell disease, the HbS mutation (c.20A>T) is the most common, primarily linked to the Arab-Indian haplotype, whereas polymorphisms in BCL11A, HBS1L-MYB, and ANTXR1 influenced fetal hemoglobin levels.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “A Comprehensive Review of Gene Mutations in Inherited Blood Disorders Among the Saudi Population. BACKGROUND: Inherited blood disorders (IBDs) are a major health concern in the Kingdom of Saudi Arabia (KSA), largely due to the high prevalence of consanguineous marriages. OBJECTIVES: This review is aimed at summarizing gene mutations and variants associated with IBDs in the Saudi population to enhance diagnosis and personalized care. METHODS: Published studies on IBD-related genetic mutations in Saudis were systematically retrieved from PubMed, Web of Science, Google Scholar, and EGEMS database using keywords "gene," "Saudi," "polymorphism," and "the different inherited blood disorders." A total of 118 studies published between 2015 and 2024 met the inclusion criteria. CONCLUSION: The Saudi population exhibits a distinct and diverse spectrum of IBD-related mutations.” | 0.95 | saudi_context_rules_v1 |
| variant | c.20A>T | “In sickle cell disease, the HbS mutation (c.20A>T) is the most common, primarily linked to the Arab-Indian haplotype, whereas polymorphisms in BCL11A, HBS1L-MYB, and ANTXR1 influenced fetal hemoglobin levels.” | 0.95 | hgvs_regex_v1 |