Characterization of Two Deep Intronic Variants on the -Globin Gene with Inconsistent Interpretations of Clinical Significance
| Autor: | Cornelis L. Harteveld, Bente Fjeld, Sandra G.J. Arkesteijn, Runa M. Grimholt, Olav Klingenberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
In silico Clinical Biochemistry beta-Globins Biology Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Humans Gene Genetics (clinical) Sequence (medicine) Genetics Messenger RNA sequence variants Base Sequence interpretations beta-Thalassemia Biochemistry (medical) deep intronic variants Intron Genetic Variation Hematology Phenotype Introns 030104 developmental biology Regulatory sequence RNA splicing beta-Globin gene beta-thalassemia (-thal) 030215 immunology |
| Zdroj: | Hemoglobin, 42(2), 126-128 |
| ISSN: | 0363-0269 |
| DOI: | 10.1080/03630269.2018.1473255 |
| Popis: | Sequence variants located in the introns of the β-globin gene may affect the mRNA processing and cause β-thalassemia (β-thal). Sequence variants that change one of the invariant dinucleotides at the exon-intron boundaries may have fatal consequences for normal mRNA splicing. Intronic variants located far from obvious regulatory sequences can be more difficult to evaluate. There is a potential for misinterpretation of such sequence variants. Hence, thorough evaluation of patient data together with critical use of databases and in silico prediction tools are important. Here, we describe two rare sequence variants in the second intron of the β-globin gene, HBB: c.316-70C>G and HBB: c.316-125A>G (NM_000518.4), both previously reported as variants causing β-thal, and later as benign sequence variants. Due to the limited number of published cases and inconsistent interpretations, the significance of these sequence variants has been unclear. We have identified these two sequence variants in multiple individuals, alone and in a variety of combinations with other δ- and β-globin defects, and we find no influence of the sequence variants on the phenotype. |
| Databáze: | OpenAIRE |
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