Characterization of Two Deep Intronic Variants on the ß-Globin Gene with Inconsistent Interpretations of Clinical Significance.
Hemoglobin
; 42(2): 126-128, 2018 Mar.
Article
em En
| MEDLINE
| ID: mdl-30047296
ABSTRACT
Sequence variants located in the introns of the ß-globin gene may affect the mRNA processing and cause ß-thalassemia (ß-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 ß-globin gene, HBB c.316-70C>G and HBB c.316-125A>G (NM_000518.4), both previously reported as variants causing ß-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 ß-globin defects, and we find no influence of the sequence variants on the phenotype.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Íntrons
/
Polimorfismo de Nucleotídeo Único
/
Globinas beta
Limite:
Humans
Idioma:
En
Revista:
Hemoglobin
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Noruega