Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Causes of Abnormal Hemoglobin Electrophoresis / 中国实验血液学杂志

OBJECTIVE@#To investigate the possible causes of abnormal hemoglobin electrophoresis results.@*METHODS@#The hemoglobin electrophoresis results of 5 696 patients in the First Affiliated Hospital of Chengdu Medical College from September 2018 to July 2021 were collected, and the abnormal results and clinical significance were analyzed.@*RESULTS@#The results of 486 patients (accounting for 8.53%) were abnormal, of which 300 cases had increased HbA2, 135 cases had decreased HbA2, 44 cases had increased F alone, and 7 cases had abnormal hemoglobin bands. Among the 486 patients, 246 patients were thalassemia gene positive (the positive rate was 50.62%), including 29 cases of α thalassemia, 208 cases of β thalassemia and 9 cases of αβ thalassemia. Among the patients with elevated HbA2, 68.67% were detected β thalassemia, 3.00% αβ thalassemia, 9.33% were suspected to be caused by macrocytosis, 6.33% by thyroid dysfunction, and 12.67% by uncertainty of the method. Among the patients with reduced HbA2, 21.48% were detected α thalassemia, 60.00% iron deficiency anemia, 8.15% were suspected to be caused by thyroid dysfunction, and 10.37% by uncertainty of the method. Among the patients with elevated F alone, the results of thalassemia gene detection were negative, 40.91% of them were suspected to be caused by macrocytosis, 27.27% by hereditary persistence of fetal hemoglobin, 29.55% by special physiological condition of pregnant women, and 2.27% by hyperthyroidism. Abnormal hemoglobin bands were detected in 7 patients, including 4 cases of hemoglobin D, 2 cases of hemoglobin E, and 1 case of hemoglobin J.@*CONCLUSION@#Thalassemia, iron deficiency anemia, macrocytosis such as megaloblastic anemia and non-severe aplastic anemia, thyroid dysfunction, hereditary persistence of fetal hemoglobin, abnormal hemoglobin diseases, the uncertainty of the method are all important causes of abnormal hemoglobin electrophoresis results. In clinical work, the patient's indicators should be comprehensively analyzed to determine the possible cause.

Clinical Diagnosis and Prenatal Screening of Hb Lepore-BW Associated with IVS-II-654 Heterozygous Mutation / 中国实验血液学杂志

OBJECTIVE@#To identify one case of rare Hb Lepore-BW associated with IVS-II-654 heterozygous mutation in Sichuan area.@*METHODS@#The blood routine examination and hemoglobin electrophoresis methods were used to analyze the blood routine parameters, HbA2 and HbF in the samples of peripheral blood in proband and his parents, as well as the cord blood of pregnant woman. The detection of thalassemia gene and Sanger sequencing methods were used to detect the hemoglobin mutations.@*RESULTS@#The result showed that the Hb Lepore-BW heterozygous mutation was detected in the father of the proband, while a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation was detected in the proband, as well as his mother and cord blood were both detected as IVS-II-654 heterozygous mutation.@*CONCLUSION@#The study identified a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation, which was characterized by intermediate β-thalassemia. It is necessary to hemoglobin electrophoresis combined with routine blood testing in prenatal screening.

Analysis of neonatal abnormal hemoglobinopathy in Wuhan and its surrounding areas / 中华地方病学杂志

Objective:To analyze the incidence and characteristics of neonatal abnormal hemoglobinopathy in Wuhan and its surrounding areas.Methods:Dry blood spot samples of newborns (born from January 2020 to June 2021) sent to Hubei Neonatal Disease Screening Center were tested by hemoglobin capillary electrophoresis, and the newborns with abnormal hemoglobin bands were further tested for gene and statistically analyzed.Results:A total of 51 348 samples of neonatal dry blood spots were collected. According to electrophoresis analysis, abnormal bands were detected in 127 cases, and 78 cases were recalled for genetic test, the recall rate was 61.42%. Among them, 42 cases were diagnosed as abnormal hemoglobinopathy. Calculated according to the recall ratio, the detection rate of abnormal hemoglobinopathy was 0.13%. There were 11 cases of α-globin chain structural variation, most often were 3 cases of Hb Queens (27.27%) and 2 cases of Hb I (18.18%); moreover, there were 31 cases of β-globin chain structural variation, among which 11 cases of Hb J-Bangkok (35.48%), 8 cases of Hb E (25.81%) and 7 cases of Hb New York (22.58%) appeared more frequently. Among the 13 kinds of abnormal hemoglobins found, Hb I was located in N13/N(Bart) zone; Hb J-Bangkok and Hb J-Meerut were located in N12 zone; Hb New York and Hb Shenyang were located in N11 zone; Hb G-Coushatta, Hb G-Taipei and Hb Port Phillip were located in N5/N(D/G/K) zone; Hb Queens, Hb G-Honolulu and Hb Ottawa were located in N4/N(S) zone; Hb Montgomery and Hb E were located in N3/N (E) zone.Conclusion:The incidence of neonatal abnormal hemoglobinopathy in Wuhan and its surrounding areas is low, and main type of abnormal hemoglobin is β-globin chain structural variation.

Clinical and genetic analysis of a patient with Hb Ottawa in conjunction with β-thalassemia / 中华医学遗传学杂志

Objective@#To analyze the hematological characteristics of a patient with Hb Ottawa in conjunction with β-thalassemia.@*Methods@#Peripheral blood samples from the proband and her parents were collected and subjected to red blood cell analysis and hemoglobin electrophoresis. Genotypes of α- and β-globin genes were also analyzed.@*Results@#The proband and her mother were both heterozygotes for Hb Ottawa and β-thalassemia variant IVS II-654, and presented with typical β-thalassemia trait featuring hypochromic microcytic anemia. An abnormal hemoglobin band was detected upon electrophoresis.@*Conclusion@#Co-existence of Hb Ottawa and β-thalassemia may not aggravate the phenotype.

Anemia hemolítica grave causada por hemoglobina Southampton: Presentación de caso clínico / Severe hemolytic anemia due to hemoglobin Southampton: Case report

Las hemoglobinopatías estructurales son variantes de la hemoglobina caracterizadas por la síntesis de una molécula cualitativamente diferente de la normal. La mayoría son inocuas, mientras que otras ocasionan cambios fisicoquímicos que determinan manifestaciones clínicas de gravedad variable. En el caso de las hemoglobinas inestables, las alteraciones reducen la solubilidad y facilitan la formación de complejos de hemoglobina desnaturalizada (cuerpos de Heinz) que precipitan, lo cual daña la membrana y destruye prematuramente al eritrocito. Hasta la actualidad se han descrito 142 hemoglobinas inestables, muchas de ellas ocasionan hemólisis crónica, que puede exacerbarse por infecciones o por la ingesta de medicamentos o drogas oxidantes. La hemoglobina Southampton (también conocida como hemoglobina Casper) es una variante inestable que resulta de la sustitución de un residuo de leucina por uno de prolina, en el codón ß106 (CTG ?CCG, como consecuencia de la mutación c.320 T>C. Presentamos una niña con anemia hemolítica grave, esplenomegalia y requerimiento transfusional debidos a hemoglobina Southampton.

Variant hemoglobins are the result of different types of mutations that occur in the globin genes. In many cases, these hemoglobinopathies are harmless, while in others they determine alterations in the physical and chemical properties raising clinical manifestations of variable severity. In the unstable hemoglobinopathies, the changes reduce solubility, inducing the formation of precipitates of denaturated hemoglobin (Heinz bodies), which damage the membrane and finally destroy the red blood cells prematurely. Up to now, more than 142 different unstable hemoglobins have been described, most of them cause chronic hemolysis, increased by infections or drugs. We report the clinical presentation of an unstable hemoglobin (hemoglobin Southampton) in a girl with severe hemolytic anemia, splenomegaly and red blood cell requirement.

Compound heterozygosity of Hb Q India (α64 (E13) ASP→HIS) and -α3,7 thalassemia. First report from Argentina / Heterocigosis de la Hb Q India (α64 (E13) ASP →HIS) y -α3,7 thalassemia. Primer informe desde Argentina

Hemoglobine (Hb) Q-India is an innocuous αglobin variant: α64 Asp → His. DNA sequencing studies have shown that the Hb Q India mutation is GAC → CAC in codon 64 of the α1 gene. Hb Q-India is a well-known hemoglobin variant in South-East Asia but only isolated case reports exist in literature to describe this rare entity in the rest of de world. The variant has been found with various forms of αand ß thalassemia. This hemoglobin has the same electrophoretic mobility as Hb S. We report, for the first time, the identification of Hb Q-India in an Argentinian woman (her parents came from Gibraltar), referred to our laboratory bearing a mild microcytic hypocromic anemia; a co-inherited α+ thalassemia (-α3.7 th) was also found.

La hemoglobina (Hb) Q India es una hemoglobina anormal e inocua que afecta la cadena α de esta. Los análisis de secuencia han demostrado que la mutación se encuentra en el codon 64 GAC → CAC del gen α1. Si bien es una variante muy conocida en el sudeste asiático, solo se han reportado pocos casos en el resto del mundo. Esta hemoglobina anormal se ha encontrado asociada con diversas formas de α y ß talasemia y su posición electroforética es idéntica a la de la Hb S. Reportamos, por primera vez, la identificación de la Hb Q India en una mujer Argentina (cuyos padres procedían del Peñón de Gibraltar), enviada a nuestro laboratorio por padecer de anemia microcítica hipocrómica, en la que se encontró también la coexistencia de α+ talasemia (-α3,7 th).

Interação entre Hb B2 e Hb S / Interaction between Hb B2 and Hb S

As hemoglobinopatias e talassemias constituem as afecções genéticas mais comuns, apresentando-se, na maioria dos casos, em heterozigose. Diante da diversidade de hemoglobinas variantes encontrada na população brasileira, metodologias específicas e complementares para um diagnóstico laboratorial preciso, capaz de elucidar possíveis interações entre estas variantes genéticas, são necessárias. Este relato de caso descreve a interação entre hemoglobina B2 e a hemoglobina S em um indivíduo do sexo feminino, caucasoide, proveniente da região Sudeste do Brasil, identificada por meio de técnicas eletroforéticas em diferentes pH, cromatografia líquida de alta performance e PCR- RFLP. Visto que a hemoglobina B2 coelui com a hemoglobina S na análise cromatográfica e dificilmente é visualizada em eletroforese pH alcalino, devido à sua baixa concentração, justifica-se a necessidade da associação de testes laboratoriais, inclusive moleculares, na rotina do diagnóstico de hemoglobinas para a correta identificação do perfil de hemoglobinas do indivíduo e real frequência na população brasileira. Rev. Bras. Hematol. Hemoter.

Hemoglobinopathies and thalassemias are the most common genetic diseases, and in most cases, present as heterozygous. Due to the diversity of hemoglobin variants, specific and complementary methodologies are necessary for a precise laboratorial diagnosis, able to elucidate possible interactions between genetic polymorphisms. This case report describes an interaction between hemoglobin B2 and hemoglobin S in a Caucasian woman from the southeastern region of Brazil. This interaction was identified by electrophoresis in different pHs, high performance liquid chromatography and PCR-RFLP. As hemoglobin B2 is eluted in the same window as hemoglobin S in automatic HPLC systems and is hardly seen in alkaline electrophoresis due to its low concentration, the association must be confirmed using additional laboratorial tests, including molecular biology techniques. These tests should be included in the routine practice of hemoglobinopathy diagnosis in order to correctly identify hemoglobin variants and to know the real frequency of these mutations in the Brazilian population. Rev. Bras. Hematol. Hemoter.

Chemical Structural Analysis of the First Case of Hb G-TaiBei ?22(B4)Glu-Gly in the Naxi Nationality / 昆明医科大学学报

In this paper,the structural analysis of a case of Hb TaiBei ?22(B4)Glu-Gly found in the Naxi nationality in Yunnan Province was described.This is the first case of Hb variant found in this nationality.

Screening of Abnormal Hemoglobin Among People of Hani and Yi Minority Nationalities in Honghe Yunnan / 昆明医科大学学报

The resuets of the screening of abnormal Hb among people of Hani and Yi minority nationalitios in Honghe, Yunnan were reported in this paper, It was found that the inci- dence of abnormal Hb in This area was 1.25%, By studying the types of abnormal Hb, we found that the main abnormal Hb in Hani and Yi minority nationalities was Hb E. In addi- tion, a slow-mouing Hb was found, Primary structural analysis showed that it was a ?-Chaim variant designated as Hb G-Yuanyang (?43 (CD2) Glu-Gly),. it is a new vari- ant type of abnormal Hb found and reported for the first time in Yunnan, China.