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1.
Pan Afr Med J ; 48: 10, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946743

RESUMO

Introduction: the utility of glycated haemoglobin (HbA1c) for the diagnosis and monitoring of diabetes in sub-Saharan Africa is uncertain due to limited data on the performance of the available HbA1c assay methods in this population, which has a high prevalence of haemoglobin variants. We aimed to compare the diagnostic accuracy of the major HbA1c methodologies (Boronate Affinity, Capillary Electrophoresis, High Performance Liquid Chromatography, Immunoassay) in an African population, and assess the impact of the common haemoglobin variant HbAS (sickle cell trait). Methods: whole blood samples were obtained from 182 individuals living with type 2 diabetes in Uganda. HbA1c values for each method were compared to average glucose measured over 14 days by continuous glucose monitoring (CGM). To determine concordance, the three HbA1c assay methods were compared to the capillary electrophoresis method. Results: there was a strong correlation between CGM average glucose levels and all four HbA1c methodologies (r=0.81-0.89) which did not differ in those with and without HbAS (present in 37/182 participants). The presence of HbAS did not alter the relationship between HbA1c and CGM glucose for any assay (p for interaction >0.2 for all methods). Diagnostic accuracy for CGM average glucose thresholds of 7 and 10mmol/L was similar across methods (area under the receiver operating characteristic curve 0.80-0.84 and 0.76-0.84 respectively). The maximum bias between the HbA1c assay methodologies was 2 mmol/mol (2.07%). Conclusion: all major HbA1c technologies offer accurate and comparable HbA1c measurement even in this population with high prevalence of haemoglobin variants.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Eletroforese Capilar , Hemoglobinas Glicadas , Sensibilidade e Especificidade , Humanos , Hemoglobinas Glicadas/análise , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Eletroforese Capilar/métodos , Feminino , Glicemia/análise , Masculino , Pessoa de Meia-Idade , Cromatografia Líquida de Alta Pressão/métodos , Uganda , Adulto , Imunoensaio/métodos , Imunoensaio/normas , Automonitorização da Glicemia/métodos , Idoso , Hemoglobinas Anormais/análise
2.
Clin Lab ; 70(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38965958

RESUMO

BACKGROUND: New hemoglobin (Hb) variants are constantly being updated as assays are developed and the testing population expands. Here, we report a novel Hb variant, named Hb Guigang. METHODS: Hemoglobin (Hb) analysis was analyzed by capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). Glycated hemoglobin was performed by CE and HPLC. Routine genetic analysis was done with Gap-PCR and PCR-reverse dot-blot hybridization. The hemoglobin variant was identified by Sanger sequencing. RESULTS: CE of three cases showed the presence of Hb variants in Zone 5 and Zone 12, respectively. HPLC indicated an elevated P3 peak, suggesting the possible presence of the Hb variant. Hb A1c was measured by CE and HPLC, and the results were 6.7% and 4.76%, respectively. Sanger sequencing confirmed an AAG˃AAT mutation at codon 90 of the HBA1 gene. This mutation was reported for the first time, and we named it Hb Guigang based on the proband's place of residence. CONCLUSIONS: Hb Guigang with normal hematological parameters was separated and quantified by CE, whereas HPLC suggested that Hb Guigang co-eluted with the P3 peaks and could not be quantified.


Assuntos
Eletroforese Capilar , Hemoglobinas Glicadas , Hemoglobinas Anormais , alfa-Globinas , Humanos , Hemoglobinas Anormais/genética , alfa-Globinas/genética , Cromatografia Líquida de Alta Pressão , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Masculino , Feminino , Mutação , Análise Mutacional de DNA , Adulto
3.
Int J Mol Sci ; 25(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38928486

RESUMO

Haemoglobin disorders represent a heterogeneous group of inherited conditions that involve at least one genetic abnormality in one or more of the globin chains, resulting in changes in the structure, function, and/or amount of haemoglobin molecules, which are very important for their related clinical aspects. Detecting and characterizing these disorders depends primarily on laboratory methods that employ traditional approaches and, when necessary, newer methodologies essential for solving a number of diagnostic challenges. This review provides an overview of key laboratory techniques in the diagnosis of haemoglobinopathies, focusing on the challenges, advancements, and future directions in this field. Moreover, many haemoglobinopathies are benign and clinically silent, but it is not uncommon to find unexpected variants during routine laboratory tests. The present work reported a rare and clinically interesting case of identification of haemoglobin fractions in an adult man by the determination of glycated haemoglobin (HbA1c) during a routine laboratory assessment, highlighting how the correct use of laboratory data can modify and improve the patient's clinical management.


Assuntos
Hemoglobinopatias , Técnicas de Diagnóstico Molecular , Humanos , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinopatias/sangue , Técnicas de Diagnóstico Molecular/métodos , Hemoglobinas/genética , Hemoglobinas/análise , Masculino , Hemoglobinas Glicadas/análise , Hemoglobinas Anormais/genética
4.
J Med Case Rep ; 18(1): 279, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38877536

RESUMO

BACKGROUND: Glycated hemoglobin is a well-known marker for evaluating long-term glycemic control. However, the accuracy of glycated hemoglobin measurement can be affected by the presence of hemoglobin variants, which makes the determination and interpretation of glycated hemoglobin values in terms of glycemic control not only difficult but also misleading. Here we present the first ever case of a patient with type 2 diabetes with hemoglobin E from Nepal, diagnosed incidentally because of spurious glycated hemoglobin levels. CASE PRESENTATION: A 45-year-old Hindu Mongolian female with a history of type 2 diabetes for around 9 years but not very compliant with follow-ups was referred to our facility for plasma fasting and postprandial blood glucose levels and glycated hemoglobin. Fasting and postprandial blood sugars were found to be high. A consistent very low glycated hemoglobin by two different high-performance liquid chromatography (HPLC) methods compelled us to call the patient for a detailed clinical history and for the records of investigations done in the past. The patient has been a known case of type 2 diabetes for around 9 years and presented irregularly for follow-up visits. Around 4 years ago, she presented to a healthcare facility with fatigue, severe headaches, pain in the abdomen, discomfort, and dizziness for a couple of months, where she was shown to have high blood glucose. She was referred to a tertiary-level hospital in Kathmandu, where she was prescribed metformin 500 mg once daily (OD). Due to her abnormal hemoglobin A1c reports, she was then sent to the National Public Health Laboratory for repeat investigations. Her blood and urine investigations were sent. Complete blood count findings revealed high red blood cell and white blood cell counts, a low mean corpuscular volume, and a high red cell distribution width-coefficient of variation. Other parameters, including serum electrolytes, renal function tests, liver function tests, and urine routine examinations, were within normal limits. A peripheral blood smear revealed microcytic hypochromic red cells with some target cells. Hemoglobin electrophoresis showed a very high percentage of hemoglobin E, a very low percentage of hemoglobin A2, and normal proportions of hemoglobin A and hemoglobin F. A diagnosis of homozygous hemoglobin E was made, and family screening was advised. CONCLUSIONS: Clinicians should be aware of the limitations of glycated hemoglobin estimation by ion exchange high-performance liquid chromatography in patients with hemoglobin E and other hemoglobin variants. If the clinical impression and glycated hemoglobin test results do not match, glycated hemoglobin values should be determined with a second method based on a different principle, and glycemic status should be confirmed through alternative investigations, preferably those that are not influenced by the presence of hemoglobin variants (for example, boronate affinity chromatography, fructosamine test, glycated albumin test, the oral glucose tolerance test, continuous glucose monitoring, etc.). Consistent or even doubtful results should also raise the suspicion of a hemoglobin variant, which should be confirmed through further evaluation and investigations.


Assuntos
Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Hemoglobinas Anormais , Achados Incidentais , Humanos , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Pessoa de Meia-Idade , Hemoglobinas Glicadas/análise , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/análise , Glicemia/metabolismo , Hipoglicemiantes/uso terapêutico
5.
Sci Rep ; 14(1): 9966, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38693200

RESUMO

Hemoglobin (Hb) Lepore is a rare deletional δß-thalassemia caused by the fusion between delta-beta genes, and cannot be identified by traditional thaltassemia gene testing technology. The aim of this study was to conduct molecular diagnosis and clinical analysis of Hb Lepore in four unrelated Chinese families using third generation sequencing. Decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and an abnormal Hb band were observed in the probands of the four families. However, no common α and ß-thalassemia variants were detected in the enrolled families using polymerase chain reaction-reverse dot blot hybridization based traditional thalassemia gene testing. Further third-generation sequencing revealed similar Hb Lepore-Boston-Washington variants in all the patients, which were resulted from partial coverage of the HBB and HBD globin genes, leading to the formation of a delta-beta fusion gene. Specific gap-PCR and Sanger sequencing confirmed that all the patients carried a similar Hb Lepore-Boston-Washington heterozygote. In addition, decreased levels of MCH and Hb A2 were observed in the proband's wife of family 2, an extremely rare variant of Hb Nanchang (GGT > AGT) (HBA2:c.46G > A) was identified by third-generation sequencing and further confirmed by Sanger sequencing. This present study was the first to report the similar Hb Lepore-Boston-Washington in Chinese population. By combining the utilization of Hb capillary electrophoresis and third-generation sequencing, the screening and diagnosis of Hb Lepore can be effectively enhanced.


Assuntos
Povo Asiático , Hemoglobinas Anormais , Adulto , Feminino , Humanos , Masculino , Povo Asiático/genética , Globinas beta/genética , Talassemia beta/genética , Talassemia beta/diagnóstico , Talassemia beta/sangue , China , População do Leste Asiático , Hemoglobinas Anormais/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Linhagem
6.
Am J Case Rep ; 25: e943560, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38725231

RESUMO

BACKGROUND Thalassemia and hemoglobin (Hb) variants are the most common hereditary red blood cell disorders worldwide. Alpha-thalassemia and alpha-globin variants are caused by mutations of the alpha-globin genes (HBA2 and HBA1), resulting in impaired alpha-globin production and structurally abnormal globin, respectively. Clinical severity of alpha-thalassemia correlates with the number of affected alpha-globin genes, yielding a spectrum of clinical manifestations from mild to severe anemia. Routine diagnosis involves Hb analysis and PCR-based methods, yet identifying rare variants necessitates comprehensive clinical and hematologic laboratory data. The knowledge of phenotype and genotype correlation is useful for genetic counseling and treatment planning. CASE REPORT A 59-year-old Thai woman presented with chronic anemia. Her baseline Hb level ranged between 8.0 and 9.0 g/dL, with no history of transfusion. Physical examination showed mild pallor, without enlarged liver and spleen. Laboratory investigations showed microcytic, hypochromic anemia and abnormal Hb peak by Hb analysis (retention time 4.58 min by HPLC method). Common alpha-globin gene deletions, including the Southeast-Asian/Thai 3.7 kb and 4.2 kb deletions were tested using gap-PCR, with none of these deletions detected. Direct DNA sequencing revealed a compound heterozygosity of Hb Jax (HBA2: c.44G>C) and Hb Constant Spring (HBA2: c.427T>C). CONCLUSIONS Compound heterozygosity of Hb Jax and Hb Constant Spring results in microcytic anemia. Hb Jax can be identified by Hb analysis, and diagnosis can be confirmed by direct DNA sequencing method. Coinheritance of Hb Jax and alpha-globin variants should be considered in cases with microcytic anemia and a specific Hb peak seen in Hb chromatogram.


Assuntos
Anemia Hipocrômica , Hemoglobinas Anormais , Feminino , Humanos , Pessoa de Meia-Idade , alfa-Globinas/genética , Talassemia alfa/genética , Talassemia alfa/diagnóstico , Anemia Hipocrômica/genética , Hemoglobinas Anormais/genética
8.
BMC Pediatr ; 24(1): 330, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741052

RESUMO

BACKGROUND: Thalassemias represent some of the most common monogenic diseases worldwide and are caused by variations in human hemoglobin genes which disrupt the balance of synthesis between the alpha and beta globin chains. Thalassemia gene detection technology is the gold standard to achieve accurate detection of thalassemia, but in clinical practice, most of the tests are only for common genotypes, which can easily lead to missing or misdiagnosis of rare thalassemia genotypes. CASE PRESENTATION: We present the case of an 18-year-old Chinese female with abnormal values of routine hematological indices who was admitted for genetic screening for thalassemia. Genomic DNA was extracted and used for the genetic assays. Gap polymerase chain reaction and agarose gel electrophoresis were performed to detect HBA gene deletions, while PCR-reverse dot blot hybridization was used to detect point mutations in the HBA and HBB genes. Next-generation sequencing and third-generation sequencing (TGS) were used to identify known and potentially novel genotypes of thalassemia. We identified a novel complex variant αHb WestmeadαHb Westmeadαanti3.7/-α3.7 in a patient with rare alpha-thalassemia. CONCLUSIONS: Our study identified a novel complex variant that expands the thalassemia gene variants spectrum. Meanwhile, the study suggests that TGS could effectively improve the specificity of thalassemia gene detection, and has promising potential for the discovery of novel thalassemia genotypes, which could also improve the accuracy of genetic counseling. Couples who are thalassemia carriers have the opportunity to reduce their risk of having a child with thalassemia.


Assuntos
Talassemia alfa , Humanos , Talassemia alfa/genética , Talassemia alfa/diagnóstico , Feminino , Adolescente , Sequenciamento de Nucleotídeos em Larga Escala , Genótipo , Testes Genéticos/métodos , Mutação Puntual , Hemoglobinas Anormais/genética
9.
Sci Rep ; 14(1): 8894, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632453

RESUMO

To assess the diagnostic performance of three cardiothoracic (CT) ratio techniques, including diameter, circumference, and area, for predicting hemoglobin (Hb) Bart's disease between 17 and 22 weeks' gestation, and to create a multivariable scoring system using multiple ultrasound markers. Before invasive testing, three CT ratio techniques and other ultrasound markers were obtained in 151 singleton pregnancies at risk of Hb Bart's disease. CT diameter ratio demonstrated the highest sensitivity among the other techniques. Significant predictors included CT diameter ratio > 0.5, middle cerebral artery-peak systolic velocity (MCA-PSV) > 1.5 multiples of the median, and placental thickness > 3 cm. MCA-PSV exhibited the highest sensitivity (97.8%) in predicting affected fetuses. A multivariable scoring achieved excellent sensitivity (100%) and specificity (84.9%) for disease prediction. CT diameter ratio exhibited slightly outperforming the other techniques. Increased MCA-PSV was the most valuable ultrasound marker. Multivariable scoring surpassed single-parameter analysis in predictive capabilities.


Assuntos
Hemoglobinas Anormais , Talassemia alfa , Gravidez , Feminino , Humanos , Hidropisia Fetal , Placenta/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Talassemia alfa/diagnóstico , Biomarcadores
10.
Sci Rep ; 14(1): 9255, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649425

RESUMO

Data on hemoglobin (Hb) variants in southern Thailand are lacking. This study aimed to reassess the frequency of Hb variants and the clinical aspects of compound heterozygous Hb variant with other hemoglobinopathies. We enrolled 13,391 participants from ten provinces in southern Thailand during 2015-2022. Hb analysis was performed using capillary electrophoresis, and mutations in the HBA and HBB genes were identified using PCR or DNA sequencing. Hb variants were identified in 337 (2.5%) unrelated subjects. Nine ß-chain variants, namely Hb Malay (76.9%), Hb C (10.1%), Hb D-Punjab (2.9%), Hb G-Makassar (2.3%), Hb Dhonburi (2.3%), Hb Tak (1.4%), Hb J-Bangkok (1.4%), Hb New York (0.3%), and Hb Hope (0.3%), and four α-chain variants-Hb G-Georgia (HBA1) (0.9%), Hb G-Georgia (HBA2) (0.3%), Hb Q-Thailand (0.6%), and Hb St. Luke's-Thailand (0.3%)-were identified. The southern population exhibited a distinct spectrum of Hb variants compared to that observed in the populations from other areas. Several compound heterozygous genotypes were also identified. Combining Hb Malay with Hb E or high Hb F determinants did not require a blood transfusion. This study provides essential information for genetic counseling in thalassemia prevention and control programs in this region.


Assuntos
Hemoglobinas Anormais , Epidemiologia Molecular , Humanos , Tailândia/epidemiologia , Feminino , Masculino , Hemoglobinas Anormais/genética , Adulto , Pessoa de Meia-Idade , Hemoglobinopatias/genética , Hemoglobinopatias/epidemiologia , Adolescente , Mutação , Adulto Jovem , Criança , Heterozigoto , Idoso
11.
Hemoglobin ; 48(2): 129-132, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38626925

RESUMO

Alpha and Beta Thalassemia are autosomal recessive anemias that cause significant morbidity and mortality worldwide, especially in the Middle East and North Africa (MENA) region where carrier rates reach up to 50%. We report the case of two siblings of Palestinian origin born who presented to our tertiary healthcare center for the management of severe transfusion dependent hemolytic anemia. Before presentation to our center, the siblings were screened for a-thalassemia using the Alpha-globin StripAssay. They were found to carry the α2 polyA-1 [AATAAA > AATAAG] mutation in the heterozygous form, which was insufficient to make a diagnosis. No pathogenic variants were detected on Sanger sequencing of the HBB gene. Full sequencing of the a-gene revealed compound heterozygous variants (HBA1:c.119_121delCCA and the previously detected HBA2:c.*+94A > G Poly A [A->G]) with trans inheritance. This report highlights the impact of non-deletional mutations on α-globin chain stability. The compound heterozygosity of a rare α-globin chain pathogenic variant with a polyadenylation mutation in the probands leads to clinically severe a-thalassemia. Due to the high carrier status, the identification of rare mutations through routine screening techniques in our populations may be insufficient. Ongoing collaboration among hematologists, medical geneticists, and counselors is crucial for phenotypic-genotypic correlation and assessment of adequate genetic testing schemes.


Assuntos
Hemoglobinas Anormais , Irmãos , alfa-Globinas , Feminino , Humanos , Masculino , alfa-Globinas/genética , Talassemia alfa/genética , Talassemia alfa/diagnóstico , Árabes/genética , Transfusão de Sangue , Hemoglobinas Anormais/genética , Heterozigoto , Mutação , Pré-Escolar , Criança
12.
Hemoglobin ; 48(2): 133-137, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38632978

RESUMO

The first identification of a novel α1-Globin variant, Hb Ormylia in 11 Greeks originating from a small village, Ormylia, Chalkidiki, Greece is reported. The new genetic variant leads to the production of a hemoglobin variant that can be identified and quantified by High-Performance Liquid Chromatography. Capillary and classic electrophoresis were not informative. Direct DNA sequencing revealed a new mutation C > G mutation at codon 21 of α1 gene (His > Gln). The new variant has been named Hb Ormylia and this is the first description of this genetic variant of α1 gene in the literature.


Assuntos
Hemoglobinas Anormais , alfa-Globinas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , alfa-Globinas/genética , Talassemia alfa/genética , Talassemia alfa/diagnóstico , Substituição de Aminoácidos , Grécia , Hemoglobinas Anormais/genética , Mutação
13.
Hemoglobin ; 48(2): 79-86, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38565203

RESUMO

Hemoglobin (Hb) Volga is a rare, unstable ß-chain hemoglobin variant (ß27 Ala→Asp), causing chronic hemolytic anemia. This study presents two members of a Danish family, splenectomized due to Hb Volga at and with multiple thrombotic events. The proband was diagnosed with Hb Volga 9 years old and splenectomy was performed as a part of treatment. Throughout his life, he experienced multiple superficial thrombophlebitis, two episodes of distal deep venous thrombosis (DVT) on lower extremities (age 32 and 33) and a transient ischemic attack (TIA) presented as amaurosis fugax (age 51). Thrombophilia investigation was normal. The proband's son was diagnosed with Hb Volga and underwent splenectomy at the age of 6. Despite anticoagulation therapy, he suffered from multiple venous thromboembolic events in his youth and died of chronic pulmonary embolism (PE)/pulmonary hypertension combined with infection. Given the observed propensity for multiple thromboses in these two patients, a literature review was conducted investigating reported occurrence of thrombotic events in individuals with Hb Volga.Currently 25 cases of Hb Volga are reported worldwide. The clinical symptoms primarily described are related to hemolytic anemia. Splenectomy is reported in 15 patients. Thromboses have previously been reported in only three patients who were also splenectomized. These cases involved DVT and PE, myocardial infarction, and an unspecified thrombotic event. The proband represents the first reported Hb Volga case with both venous and arterial thrombotic disorders. The exact mechanism underlying thrombotic tendency in patients with Hb Volga remains unknown, but it is probably associated with splenectomy.


Assuntos
Hemoglobinas Anormais , Esplenectomia , Humanos , Esplenectomia/efeitos adversos , Masculino , Hemoglobinas Anormais/genética , Adulto , Trombose/etiologia , Trombose/diagnóstico , Pessoa de Meia-Idade , Dinamarca/epidemiologia , Trombose Venosa/etiologia , Trombose Venosa/diagnóstico , Criança , Linhagem
15.
Hematology ; 29(1): 2339559, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38626234

RESUMO

OBJECTIVES: In clinical practice, the majority of α-thalassaemia cases arise from deletions of the α-globin genes. However, a subset of cases is attributed to rare haemoglobin variants, which can manifest with borderline or normal screening results, potentially leading to missed diagnoses in clinical practice. METHODS: Blood samples were collected from family members and underwent haematological, DNA and RNA analysis. RESULTS: The five-month-old proband presented a haematological phenotype consistent with Hb H disease. The mother's haematology profile was consistent with an α-thalassaemia carrier, while the father exhibited a borderline reduction in MCV and MCH. MALDI-TOF identified an abnormal α-chain in the proband. DNA analysis revealed a novel α-globin variant (HBA2:c.175C>A, α58His>Asn, Hb DG-Nancheng) affecting the distal histidine in the family. The father and the mother had α-genotype of --SEA/αα and αDG-Nanchengα/αα, respectively; while the proband inherited both mutant alleles (--SEA/αDG-Nanchengα). Sequencing of cDNA from HBA2 gene identified an equal ratio of normal and mutant alleles. CONCLUSION: This rare case highlighted the importance of identifying rare haemoglobin variant during prenatal screening. The clinical and genetic data provides useful information on the pathogenicity of this variant and further insight into the role of distal histidine residue of α-globin.


Assuntos
Hemoglobinas Anormais , Talassemia alfa , Feminino , Humanos , Lactente , Gravidez , alfa-Globinas/genética , Talassemia alfa/diagnóstico , Talassemia alfa/genética , China , Hemoglobinas Anormais/genética , Histidina/genética , Mutação
16.
Hemoglobin ; 48(2): 121-124, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38450437

RESUMO

We report a new δ-chain hemoglobin (Hb) variant observed in a 5-year-old female living in Yulin, Guangxi, China. Capillary electrophoresis revealed splitting of the Hb A2 peak into two fractions (Hb A2 and Hb A2 variant), and the Hb A2 variant was also detected by high-performance liquid chromatography. However, it could not be detected using matrix-assisted laser desorption lonization-time of flight mass spectrometry. CD41-42 (-TCTT) heterozygosity was observed on the HBB gene by PCR and reverse dot-blot hybridization. Sanger sequencing showed a new transition (G > A) at codon 46 of the HBD gene, resulting in glycine changing to arginine. Based on the patient's place of residence, the new variant was named Hb A2-Yulin [δ46(CD5)Gly→Arg,HBD:c.139G > A].


Assuntos
Hemoglobina A2 , Hemoglobinas Anormais , Globinas delta , Humanos , Feminino , Globinas delta/genética , Pré-Escolar , Hemoglobinas Anormais/genética , Hemoglobina A2/genética , Substituição de Aminoácidos , China
17.
Hemoglobin ; 48(2): 125-128, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38500334

RESUMO

In this report, we describe a 6-year-old girl with a medical history of pallor, mild icterus, anemia, blood transfusion and abnormal hemoglobin variant analysis on capillary electrophoresis. She was referred for further analysis. DNA sequencing of the proband revealed a de novo mutation in Codon 88 (CTG > CCG) of the ß-globin gene (HBB: c.266T > C) in a heterozygous state compatible with hemoglobin Santa Ana, an unstable hemoglobin. This is the first case of Hb Santa Ana from Iran associated with moderate to severe anemia who underwent splenectomy with clinical improvement.


Assuntos
Hemoglobinas Anormais , Globinas beta , Humanos , Feminino , Hemoglobinas Anormais/genética , Criança , Irã (Geográfico) , Globinas beta/genética , Mutação , Esplenectomia , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinopatias/sangue
18.
Sci Rep ; 14(1): 6682, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509195

RESUMO

Abnormal hemoglobin anti-Lepore Hong Kong is a rare ßδ fusion variants resulting from non-homologous crossover during meiosis. Anti-Lepore Hong Kong is known to consistently exhibit significantly increased level of HbA2. In this study, we used multiplex ligation-dependent probe amplification (MLPA) and single molecular real-time (SMRT) sequencing, as well as Sanger sequencing, to identify variants in five unrelated families with abnormal elevated HbA2 level. All probands in these five families were found to be heterozygous for anti-Lepore Hong Kong. Among them, two families showed co-occurrence of ß0-thalassemia and α-thalassemia (-SEA/ or αCSα/). Heterozygotes for anti-Lepore Hong Kong displayed an average HbA2 level of 17.7% and behaved normal. However, when combined with ß0-thalassemia and α-thalassemia, the probands exhibited higher HbA2 level (30.2-40.8%) and behaved with ß-thalassemia trait. Furthermore, determination of the α/ß-mRNA ratio revealed a slight downregulation of ß-globin, similar to that of ß-thalassemia minor. Our study is the first to identify compound heterozygotes for anti-Lepore Hong Kong, ß0-thalassemia and α-thalassemia, provide valuable information for prenatal counseling.


Assuntos
Hemoglobinas Anormais , Talassemia alfa , Talassemia beta , Humanos , Gravidez , Feminino , Talassemia alfa/genética , Hemoglobinas Anormais/genética , Talassemia beta/genética , Globinas beta/genética
19.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469764

RESUMO

BACKGROUND: Normal hemoglobin is a tetrameric structure, consisting of two alpha-globin chains and two nonalpha (beta, gamma, delta) chains. Hemoglobinopathies occur when the presence of gene mutations affect the molecular structure or expression of the globin chains. METHODS: We reported the case of a 9-year-old Chinese girl who presented with abnormal low oxygen saturation values on pulse oximetry and no oximetry results were obtained during blood gas analysis (BGA). RESULTS: High-performance liquid chromatography (HPLC) and capillary electrophoresis demonstrated that the presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin Titusville, was proven by gene sequencing. The patient's mother and aunt also carry the hemoglobin variant, representing the first Chinese family case reported. CONCLUSIONS: Hemoglobin Titusville is a rare genetic hemoglobin structural defect. early diagnosis can help patients and clinicians avoid unnecessary anxiety and costly or excessive clinical investigations.


Assuntos
Hemoglobinopatias , Hemoglobinas Anormais , Feminino , Humanos , Criança , Saturação de Oxigênio , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Oximetria , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/análise , Oxigênio , Gasometria
20.
Int J Lab Hematol ; 46(3): 434-450, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38504512

RESUMO

The hemoglobin (Hb) variants are qualitative abnormalities due to production of structurally abnormal globin proteins. They are categorized based on the type of mutation present in the α1, α2, ß, Gγ, Aγ and δ globin genes. So far, more than 1550 Hb variants are reported in the database. They could lead to Hb polymerization, Hb instability, altered oxygen affinity and decreased oxygen-carrying capacity of Hb or have no clinical manifestations. In India, ethnic diversity, consanguinity, regional variations and migration result in the presence of different Hb variants. We have compiled all the variants of α, ß and δ globin chains in heterozygous, homozygous and in compound heterozygous forms reported from India in the last 52 years. Of the 63 rare and novel hemoglobin variants reported from India, 22 were α-globin chain variants, 37 were ß-globin chain variants and 4 were δ-globin chain variants. Twelve novel Hb variants (Hb J Rajappan, Hb Koya Dora, Hb Rampa, Hb Godavari, Hb Chandigarh, Hb D Agri, Hb Lucknow, Hb Vellore, Hb Midnapore, Hb Bijnor, Hb A2Tianhe and Hb A2Saurashtra) were identified among persons of Indian origin. Majority of them were picked up on HPLC. Some of the variants like Hb Titusville, Hb Shimonoseki, Hb Chandigarh, Hb D Agri, Hb Yaizu and Hb Vellore eluted in the HbS window whereas variants like HbD Iran, Hb St. Louis, Hb G Coushata, HbM Saskatoon, Hb Lucknow, Hb Grange-Blanche and Hb Tianshui showed falsely elevated HbA2. Hence, careful and systematic investigations are required to identify them.


Assuntos
Hemoglobinas Anormais , Humanos , Etnicidade/genética , Variação Genética , Hemoglobinopatias/genética , Hemoglobinopatias/diagnóstico , Hemoglobinas Anormais/genética , Índia , Mutação
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