The hyper-methemoglobinemia causes the oxygen transfer disorder. The clinical symptoms depends on the level of methemoylobinemia. Hypermethemoglobinemia can be congenital or acquired hypermethemoglobinemia. The congenital hypermethemoglobinemia caused by partial or total methemoglobine reeducates deficiency in patients with rare genetic heterozygous enzyme deficiency due to the abnormal hemoglobin. The acquired hypermethemoglobinemia occurred after exposure to colour compound, food and drinking water with nitrate or drugs. The determination of causative agent of hypermethemoglobin help treating more effectively
Methemoglobin ; Hemoglobins, Abnormal ; Therapeutics ; Methemoglobinemia

Humans ; Hemoglobinopathies ; Hemoglobins, Abnormal/genetics*

Humans ; Hemoglobinopathies ; Hemoglobins, Abnormal/genetics* ; Oxygen

Hemoglobins, Abnormal ; Humans ; Singapore/epidemiology* ; alpha-Thalassemia

Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.
Blastocyst ; CRISPR-Cas Systems ; Hemoglobins, Abnormal ; genetics ; metabolism ; Humans ; Zygote

OBJECTIVE: To explore the abnormal hemoglobinopathy in couples of child-bearing age in Chongqing. METHODS: A total of 34 800 subjects of child-bearing age were screened for thalassemia by using capillary electrophoresis from January 2015 to September 2018. PCR-flow cytometry fluorescence hybridization assay was used to detect the common thalassemia gene deletions and mutations. RESULTS: 8 kinds of abnormal hemoglobinopathy were detected in 200 cases from 34 800 subjects of child-bearing age, the detection rate was 0.57% in couples of child-bearing age in Chongqing: Among 200 cases of abnormal hemoglobin pathy, Hb E was found in 90 cases (accounting for 45.0%), and Hb D in 25 cases (accounting for 12.5%). Hb NewYork was found in 25 cases (accounting for 12.5%). HbJ-bangkok was found in 25 cases (accounting for 12.5%), and Hb Q-Thailand in 16 cases (accounting for 8.0%). Hb Hope was detected in 15 cases (accounting for 7.5%). Hb S was detected in 3 cases (accounting for 1.5%). Hb Hasharon was detected in 1 case (accounting for 0.5%). The mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) of Hb E and Hb Q-Thailand were lower than normal reference intervals. CONCLUSION The detection rate of abnormal hemoglobinopathy in Chongqing is higher than the average level in China. Capillary electrophoresis can effectively screen abnormal hemoglobinopathy, which is great significant for aristogenesis and improvement of population quality.
Child ; China ; Electrophoresis, Capillary ; Hemoglobinopathies ; Hemoglobins, Abnormal ; Humans ; Thailand ; Thalassemia

OBJECTIVE: To explore the genetic basis for a child with Hemoglobin Santa Ana (Hb Santa Ana). METHODS: The child was admitted to the Children's Hospital of Chongqing Medical University on August 4, 2013 due to anemia, splenomegaly and deepening urine color for 5 years. His clinical data were collected. Peripheral blood samples of the child and his parents were collected for routine blood test. The erythrocyte parameters of the child and his parents were determined with an automatic hemocyte analyzer. The hemoglobin components of the child and his parents were detected by high-performance liquid chromatography (HPLC). Common mutations associated with thalassemia were detected by Gap-PCR and PCR-reverse dot blotting (PCR-RDB). Rare variants of the globin genes were detected by next generation sequencing (NGS), and the result was verified by Sanger sequencing. RESULTS: The child has shown mild to moderate hemolytic anemia. Routine blood test showed that he had lower hemoglobin (90 g/L) and mean corpuscular hemoglobin concentration (267 g/L) but a higher reticulocyte ratio (0.141), which indicated hypopigmented hyperplastic anemia. Analysis of hemoglobin component showed that his hemoglobin F was elevated to 10.7%, which indicated abnormal synthesis of β globin peptide chain. HPLC analysis showed an abnormal peak accounting for 4.5% of the total area. Neither of his parents was found to have abnormal results for routine blood test and hemoglobin component analysis. No common globin gene variant was detected in the child. Gene sequencing revealed that the child has harbored a heterozygous variant of HBB: c.266T>C, which was de novo in origin. Based on the guidelines of American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic. CONCLUSION The heterozygous HBB: c.266T>C variant probably underlay the hemolytic anemia associated with Hb Santa Ana in this patient.
Child ; Humans ; Male ; Chromatography, High Pressure Liquid ; Hemoglobins, Abnormal/genetics*

Chromatography, Ion Exchange ; Hemoglobins, Abnormal ; analysis ; Humans ; Male

Chromatography, Ion Exchange ; Hemoglobins, Abnormal ; analysis ; Humans ; Male

Hemoglobins, Abnormal ; Humans ; alpha-Thalassemia ; complications ; beta-Thalassemia ; complications