Hemoglobin最新文献

To determine the prevalence and molecular basis of β-thalassemia in the Northeastern Iraqi province of Kirkuk, a total of 3954 individuals attending the provincial premarital screening center were recruited. The prevalence of β-thalassemia minor among the screened individuals was found to be 3.0%, while those of Hemoglobin E, and δβ-thalassemia carrier states were 0.05%, and 0.03% respectively. Molecular characterization of the β-thalassemia mutations was achieved by multiplex PCR and reverse hybridization, followed by next generation sequencing for those left uncharacterized by the former technique. Among 19 β-thalassemia mutations identified, seven were the most frequent, namely: IVS-II-1 (G > A), codon 8/9 (+G), IVS-I-6 (T > C), IVS-I-110 (G > A), IVS-I-I (G > A), IVS-I-5 (G > C) and codon 44 (-C) accounting for 78.5% of the mutations. This study further illustrates the heterogeneity of the spectrum of β-thalassemia in different parts of Iraq, and provides an essential step to facilitate prenatal diagnosis in the setting of a future national thalassemia prevention program.

PIEZO1 (piezo-type mechanosensitive ion channel component 1) is a mechanosensitive ion channel protein. Gain-of-function variants in the PIEZO1 gene are known to cause dehydrated hereditary stomatocytosis (DHS) also termed hereditary xerocytosis. This is a rare autosomal dominant condition characterized by variable-degree anemia with a tendency toward hemolysis, erythrocyte dehydration and iron overload. While the diagnostic workflow for DHS is well-established, diagnosis is often delayed due to overlapping clinical features with other hemolytic anemias and the pleiotropic effects of PIEZO1 variants. We describe the case of a Greek patient with a compensating hemolysis since birth. DHS diagnosis was established only after a prolonged history of repeated investigations spanning from his early life to 70 years of age, when a conclusive testing was achieved.

We report a novel large α-globin gene cluster deletion in a Chinese family from the Guangxi Zhuang Autonomous Regionfor the first time. The proband was a 20-year-old male who presented with microcytic hypochromatosis. Routine genetic analysis showed none of the common mutations in theα-globin and β-globin genes. Multiplex ligation-dependent probe amplification (MLPA) of the α-globin chain revealed there was a large deletion, which removed the entire HBA2 and HBA1 genes, HBQ gene, HBZ gene, and major regulatory element HS-40, eliminating more than 134 kb from the α-globin chain. Subsequently, pedigree analysis revealed that the proband inherited the novel deletion from his father. By consultation of literature and databases, it was confirmed as a hitherto undescribed chain deletion and named Laibin deletion (-^LB) for the origin of the proband.

We report a novel mutation on α2-globin gene leading to an elongated α-chain. This novel frameshift mutation was detected in a 13-year-old boy from Balkh province, Afghanistan. DNA analysis identified an insertion of thymine (T) at codon 132 [HBA2:c.396dup (p.Val134fs)]. We named the novel hemoglobin variant 'Hemoglobin Balkh' after the geographic location from which the patient originated. This novel variant was found in association with α3.7 kb α-globin gene deletion, suggesting a compound heterozygous state that contributes to the patient's clinical presentation.

Congenital hemolytic anemia (CHA) is defined as the premature destruction of red blood cells (RBC) due to congenital or acquired defects. The hereditary form of hemolytic anemia can be divided into hemoglobinopathies, membranopathies, and enzymopathies. Hereditary spherocytosis (HS) is the most common inherited RBC membranopathy leading to congenital hemolytic anemia. To date; five genes have been associated with HS coding for cytoskeleton and transmembrane proteins, those genes are SPTB, SLC4A1, EPB42, ANK1, and SPTA1. Due to genetic heterogeneity, clinical exome sequencing (CES) was performed on four unrelated Moroccan patients referred for CHA investigation. Sanger sequencing and qPCR were performed to confirm CES results and to study the de novo character of identified variants. The molecular analysis revealed 3 novel mutations and one previously reported pathogenic variant of the SPTB gene confirming the diagnosis of HS in the four patients. Hereditary spherocytosis anemia is a genetically heterogenous disease which could be misdiagnosed clinically. The introduction of novel sequencing technologies can facilitate accurate genetic diagnosis, allowing an adapted care of the patient and his family.

We report the discovery of a novel β-globin gene variant, Hb Odder, characterized by a single nucleotide substitution; HBB:c.316C > G; CD105 (Leu > Val). This variant emerged incidentally during routine HbA1c measurements for diabetes monitoring. The patient exhibited no clinical or biochemical evidence of anemia or hemolysis. Our data on this variant suggest that Hb Odder is benign, regrettably limitations in our data make formal evaluations of stability and oxygen affinity impossible; additionally this emphasizes the importance of considering hemoglobin variants in the differential diagnosis of abnormal Hb A1c levels and suggest that laboratories should use alternative methods for the correct measurement of Hb A1c when hemoglobin variants interfere with diabetes monitoring. Notably, three other mutations have been described at codon 105 of the β globin chains and correspond to three Hb variants with different characteristics: Hb South Milwaukee, Hb Bellevue IV and Hb St. George.

Hemoglobin (Hb) H disease presents a wide range of clinical phenotypes, from asymptomatic to severe forms, depending on significant genetic heterogeneity. This is the first report of clinical and hematological features of the nondeletional HbH disease caused by --^CR/α^CSα. A baby was born to a father and a mother with --^CR and α^CSα carriers, respectively. She had severe symptomatic hypochromic microcytic anemia at 2 months of age with Hb 7.8 g/dL, packed cell volume (PCV) 0.27 L/L, mean corpuscular volume (MCV) 64.3 fL, and mean corpuscular Hb (MCH) 18.3 pg. The Hb analysis using capillary electrophoresis (CE) showed Hb Bart's, HbH, and Hb CS peaks at 17.1%, 2.2%, and 1.6%, respectively. A better understanding of a patient's clinical and hematological features with --^CR/α^CSα is useful for hemoglobinopathy counseling for the national thalassemia controlling program.

Beta thalassemia is one of the monogenic disorders characterized by decreased production of β-globin chains and various types of mutations have been reported to cause thalassemia phenotype. On the other hand, rare mutations also affect and diversify the disease spectrum. Herein, we present an anemic patient from Turkey diagnosed with dominant β thalassemia due to a heterozygous mutation in exon 3 of the HBB gene.

We report the molecular and hematological identifications of two novel δ-globin gene mutations found in Guangxi Zhuang Autonomous Region, China. Capillary electrophoresis of the proband showed 1.3% Hb A₂, accompanied by a minor unknown peak (0.7%) within the Z1 zone. High-performance liquid chromatography also revealed the presence of 1.5% Hb A₂ and a 0.6% unknown peak. Routine genetic testing (Gap-PCR and reverse dot-blot hybridization) for common α-thalassemia was performed, and no mutations were observed. Sanger sequencing identified a heterozygous mutation for GAC > AAC at codon 79 (HBD:c.238G > A) and G > A at polyA + 70 (HBD:c.*200G > A) of the δ-globin gene. This variant was named Hb A₂-Guangxi [δ79 (EF3) Asp→Asn, HBD:c.238G > A] after the geographic origin of the proband.