Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α + -thalassemia in a Thai family.

Autor: Panyasai S; Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand., Khongthai K; Health Promoting Hospital, Chiang-Mai, Thailand., Satthakarn S; Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand.
Jazyk: angličtina
Zdroj: Annals of medicine [Ann Med] 2023; Vol. 55 (2), pp. 2264174. Date of Electronic Publication: 2023 Oct 05.
DOI: 10.1080/07853890.2023.2264174
Abstrakt: Background: An increasing number of α-hemoglobin (Hb) variants is causing various clinical symptoms; therefore, accurate identification of these Hb variants is important.
Objective: This study aimed to describe the molecular and hematological characteristics of novel Hb Doi-Saket that gives rise to a typical α + -thalassemia phenotype in carriers with and without other hemoglobinopathies.
Materials and Methods: Biological samples from a proband and his family members were analyzed. Hematological profiles were analyzed using a standard automated cell counter. Hb was analyzed by capillary electrophoresis and high-performance liquid chromatography. Mutations and globin haplotype were identified by DNA analysis. Novel diagnostic tools based on allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism were developed.
Results: Hb analysis showed a major abnormal Hb fraction, moving slower than HbA, and a minor Hb fraction alongside HbA 2 in the proband, his father, and son. DNA analysis of the α-globin gene identified the -α 3.7 deletion and in cis the C > A mutation on codon 9 of the α2α1 gene, corresponding to Hb Doi-Saket [α9(A7) Asn > Lys]. This mutation could be identified using newly developed allele-specific PCR-based assays. The Hb Doi-Saket al.lele was significantly associated with haplotype [- + M + + 0 -]. Interaction of α Doi-Saket with β E globin chains led to a new Hb variant (HbE Doi-Saket). Phenotypic expression was clinically silent in heterozygotes and might present slight microcytosis.
Conclusions: Hb Doi-Saket emphasizes a great diversity present in α-globin gene. The mutation in this family from Thailand was linked to -α 3.7 and caused mild microcytosis in the carriers. The combination of this variant with deletions in α genes might cause a severe clinical phenotype. Different methods of separation can provide useful information in diagnosis, and a complete molecular approach is needed for confirmation before considering patient management.
Databáze: MEDLINE
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