Hemoglobin最新文献

Hemoglobin (Hb) Lansing is a rare mildly unstable variant of α globin. Here, we report the first case of compound Hb Lansing/HbS coinherited with a single α thalassemia deletion (-alpha^3.7) in a 27-year-old woman. The patient exhibited moderate hemolytic anemia and low oxygen saturation by pulse oximetry, which failed to improve with supplemental oxygen. Notably, her oxygen saturation levels were normal by arterial blood gas. Capillary electrophoresis and high-performance liquid chromatography showed an HbS peak along with other abnormal peaks. Subsequent α globin gene sequencing revealed one copy of the -alpha^3.7 α-globin deletion and one copy of Hb Lansing variant in the alpha2-globin gene. Hemoglobin Lansing is known to cause spuriously low pulse oximetry. Additionally, the co-inheritance of the Hb Lansing and a single α thalassemia deletion may contribute to her moderate hemolytic anemia. The timely identification of hemoglobin variants is crucial for understanding the underlying cause when encountering unexpectedly low pulse oximetry, facilitating genetic counseling, and preventing unnecessary investigations and treatments. Further research is also needed to enhance our comprehension of the interactions among various hemoglobin variants; especially those associated with single a α thalassemia deletion.

Misdiagnosis of α-thalassemia genotypes due to primer site mutations presents diagnostic challenges in Chinese populations where -α^3.7 deletion and HBA2:c.427T>C (Hb Constant Spring) heterozygotes are prevalent. We describe two cases where conventional diagnostic approaches erroneously identified heterozygous carriers as homozygotes. Diagnostic algorithms employing gap-PCR and PCR-RDB for common thalassemia mutations initially suggested homozygous status in both probands. Proband 1 (28-year-old male) was misclassified as -α^3.7 homozygote by gap-PCR, but MLPA analysis revealed heterozygous status, subsequently confirmed by third-generation sequencing which identified concurrent NG_000006.1:g.32793 C > T mutation validated through Sanger sequencing. Proband 2 demonstrated discordant HBA2:c.427T > C results, with MLPA detecting atypical signal intensities in HBA2 and HBA1 loci. Comprehensive TGS analysis revealed trans configuration with HBA2:c.300+55T > G and HBA2:c.301-24delGinsCTCGGCCC variants. These cases highlight the important impact of mutations in the priming region on molecular diagnosis and emphasize the need for further characterization by other methods to avoid misdiagnosis when results from traditional methods are equivocal.

We report a novel α-thalassemia (α-thal) point mutation identified in a Chinese man with mild hypochromia and microcytosis during premarital thalassemia screening. Sanger sequencing identified a frameshift variant (HBA2:c.4delG) at codon 1 (deletion of G) in the first exon of the α2-globin gene. This genetic alteration produces a truncated α-globin chain with a premature termination codon at position 48, leading to an α⁺-thalassemia phenotype. Pedigree analysis confirmed the mutation was inherited from the paternal lineage.

α-Hemoglobin (Hb) variants are common genetic mutations worldwide. The appropriate techniques must be followed to scan and identify these variants, particularly in routine investigations for thalassemia and hemoglobinopathies in countries with high prevalence of α and β-thalassemia. High resolution melting (HRM) analysis is a popular and effective technique for identifying genetic variations with rapid output results. This study designed four newly developed primer pairs that had full coverage of the HBA genes for detection of α-Hb variants using real-time PCR with HRM analysis. Forty-one blood samples were collected from individuals with known or suspected α-Hb variants. The results demonstrated clearly distinguished melting patterns of nine α-Hb variants including Hb Constant Spring, Hb Q-Thailand, Hb Pakse', Hb Hekinan, Hb Nakhon Ratchasima, Hb Siam, Hb Thailand, Hb Queens, and Hb Quong Sze compared with the wild-type sample pattern. All mutations were confirmed by DNA nucleotide sequencing. This study presents the first case report of the combination of Hb Shaare Zedek co-inherited with Hb Hekinan in a Thai patient. Interactions between these two Hb variants displayed a high level of Hb F (23.5%) on an HPLC Hb chromatogram and a mild symptom phenotype with low mean corpuscular volume (71.3 fL) and mean corpuscular hemoglobin (21.8 pg) in the proband. Overall, HRM analysis is a suitable, rapid, and powerful technique for the identification of gene mutations, and for the diagnosis of common and rare α-Hb variants to prevent and control thalassemia in Thailand.

The commonly used methods for HbA1c measurement are cation-exchange high performance chromatography (CE-HPLC), immunologic method, capillary electrophoresis and boronate affinity HPLC. Hb-variants can reduce the reliability of HbA1c measurements. We aimed to emphasize the importance of step-by-step solutions to the difficulties encountered in HbA1c measurement methods due to Hb-variants. We also aimed to evaluate the advantages and disadvantages of different methods used in HbA1c analysis with the example of the Hb-Iraq-Halabja variant detected for the first time in Türkiye. HbA1c level could not be measured by CE-HPLC (Adams HA-8180V analyzer, Arkray, Japan) and a peak-tailing signal was detected indicating an abnormality between stable HbA1c and HbA0 peaks (concurrent glucose level was 8.55mmol/L). In the second step, HbA1c was able to be measured by immunologic method and boronate affinity method and were found to be 5.87% and 5.90%, respectively (estimated average glucose equivalent 6.66mmol/L). In the last step, genetic analysis was performed due to suspicion of Hb variant and the very rare Hb Iraq-Halabja variant was detected. After genetic verification, HbA1c test was repeated with a different CE-HPLC (HLC-723 G11, T osoh, Tokyo, Japan) and a peak indicating variant Hb was detected between stable HbA1c and HbA0. A remarkable finding was that, unlike the previous CE-HPLC (Arkray) result, HbA1c could be measured as 3.20%. In the concurrent measurement performed on the boronate affinity HPLC (Premier Hb9210, Trinity Biotech, County Wicklow, Ireland), HbA1c result was found to be 5.40% (concurrent glucose 5.22 mmol/L). In addition, concurrent fructosamine serum value was found to be 210 μmol/L (estimated mean glucose equivalent 4.88 mmol/L). The patient's laboratory tests were generally within normal limits, and iron deficiency, hemolytic anemia, and B12-folate deficiency were excluded. The glucose bounding area of hemoglobin is generally preserved and is not affected by common Hb-variants. Boronate affinity and immunologic method (these two methods target glucose bounding areas) that give HbA1c results consistent with the patient's fasting blood glucose and fructosamine results. However, the CE-HPLC method has been observed to either fail to measure HbA1c or to measure falsely low HbA1c due to overlapping peaks of Hb variants.

Backgound: Induction of fetal hemoglobin (HbF; α2γ2) production can alleviate the clinical severity of sickle cell disease (SCD) and β-thalassemia. KLF1 SNPs (e.g. rs2072597) correlate with elevated fetal hemoglobin levels in HPFH patients. Some studies suggest that KLF1 may indirectly suppress γ-globin expression by regulating the KLF1-dependent transcriptional repressor BCL11A or directly activate γ-globin. This study aims to investigate the effect of KLF1 on the γ-globin gene.

Material/methods: KLF1 was downregulated in K562 cells via RNAi, with optimized shRNA delivered by lentivirus. Additionally, an in vitro erythropoiesis model using β-thalassemia major-derived mononuclear cells (MNCs) assessed γ-globin expression. γ-globin levels were quantified by RT-qPCR and Western blot (K562) or RT-qPCR alone (erythroblasts).

Results: Knockdown of KLF1 in K562 cells significantly suppressed γ-globin expression and elevated the γ/α globin mRNA ratio in human erythrocytes, concurrent with disrupted erythroid maturation. KLF2 expression was upregulated under KLF1-deficient conditions.

Conclusions: KLF1 exhibits dual, context-dependent regulation of globin genes, acting as both activator and repressor. These findings suggest that pharmacological targeting of KLF1 may not be an optimal therapeutic strategy for β-hemoglobinopathies.

HBA2: c.70G > A (Hb Chad) and HBA1: c.84G > T (Hb Hekinan II) are extremely rare α-globin chain variants, while HBB: c.-78A > G is a relatively common mutation in β-thalassemia. This study aims to identify potential hemoglobin variants in a 12-year-old Chinese boy (proband) and evaluate the presence of thalassemia trait in his parents. We used an automated blood cell analyzer to obtain hematological data, capillary zone electrophoresis to analyze hemoglobin, and sequencing of α-globin and β-globin genes for molecular characterization. The proband exhibited typical thalassemia traits, with hemoglobin electrophoresis suggesting a complex α- and β-chain hemoglobinopathy. Genetic testing revealed that the proband was a double heterozygote for HBA2: c.70G > A (Hb Chad) and HBB: c.-78A > G, while the proband's mother was a compound heterozygote for HBA2: c.70G > A (Hb Chad) and HBA1: c.84G > T (Hb Hekinan II). This study reports for the first time two novel cases of hemoglobinopathy in a Chinese family, involving HBA2: c.70G > A (Hb Chad)/HBB: c.-78A > G and HBA2: c.70G > A (Hb Chad)/HBA1: c.84G > T (Hb Hekinan II).

Here we report a hemoglobin (Hb) variant, initially detected by matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS). A 29-year-old woman who presented to our hospital for a medical examination showed a remarkable discrepancy between her fasting plasma glucose level (5.07 mmol/L) and her HbA_1c value (3.61%), as determined by capillary electrophoresis (CE). Hemoglobin analysis by MALDI TOF MS revealed an abnormal globin with a mass of 15853 Da. Sanger sequencing identified a novel missense mutation in exon 112 of the β-globin chain [CD 112(G14) Cys > Ser (TGT > TCT); HBB:c.338G > C]. In reference to the birthplace of the proband, this variant was named Hb Jiangxi.