IF 1.2 4区医学

Hemoglobin Pub Date : 2025-06-10 DOI: 10.1080/03630269.2025.2490291

Ping Liu, Jieyu Wang, Hongyu Luo, Xue-Wei Tang, Jianying Zhou, Fan Jiang, Jin Han

{"title":"A Novel Large Deletion Including the Major Regulatory Element Compounded with SEA Deletion Causing Hydrops-Fetalis-Syndrome.","authors":"Ping Liu, Jieyu Wang, Hongyu Luo, Xue-Wei Tang, Jianying Zhou, Fan Jiang, Jin Han","doi":"10.1080/03630269.2025.2490291","DOIUrl":"https://doi.org/10.1080/03630269.2025.2490291","url":null,"abstract":"MCS-R regulatory elements are very important for the synthesis of α-globin. Deletion of the major α-globin regulatory elements compounded with deletion of α-globin genes can cause Hb Bart's (c4) hydrops fetalis, which is the severe form of α-thalassemia. In this report, a 19-year-old female at the 16th week of gestation came to our center due to abnormal fetal cardiothoracic ratio and thickened placental depth. The electrophoresis result of fetal umbilical cord blood revealed the level of Hb Bart's band to be 87.6%, which suggested the fetus was Hb Bart's hydrops fetalis. Next generation sequencing screen using targeted capture was used to detect the genotype of the fetus to be -SEA deletion, βA/βA. Multiplex ligation-dependent probe amplification (MLPA) is very useful to detect copy number variation (deletions/duplications), the result of which suggested the existence of -SEA deletion compounded with the novel large deletion of the major α-globin regulatory element (MCS-R2, R1, R3 and R4). Using the self-designed MLPA probe, the deletion should extend from the telomere downstream and the downstream breakpoint was between 143702 and 144291(GRch38/hg18). The novel deletion was also observed in the fetus' father and grandfather who had mild anemia. Of cases with the MCS deletion compounded with α0-thalassemia, this was the earliest time when the fetus presented fetal edema. Our study gave more evidence for genetic counseling for MCS deletion.","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hereditary Persistence of Fetal Hemoglobin (HPFH): Detection of Unknow ^Aγ-Globin Promoter Mutation at the C2H2 Zinc Finger Transcription Factors Binding Sites. 胎儿血红蛋白（HPFH）的遗传持久性：在C2H2锌指转录因子结合位点检测未知的a γ-球蛋白启动子突变。

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-06-08 DOI: 10.1080/03630269.2025.2514801

Maria Oggionni, Barbara Manenti

引用次数: 0

A Hemoglobin Variant, Resulting from a Novel Missense Mutation [CD 112(G14) Cys > Ser (TGT > TCT); HBB: C.338G > C], Was Discovered by MALDI-TOF MS. 一种新的错义突变[cd112 (G14) Cys > Ser (TGT > TCT)]引起的血红蛋白变异HBB: C. 338g > C]，由MALDI-TOF质谱法发现。

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-06-03 DOI: 10.1080/03630269.2025.2514134

Weijie Xie, Cheng Lin, Yueying Huang, Ziling Yang, Houlong Luo, Rong He, Xiaohui Huang, Anping Xu, Ling Ji

引用次数: 0

Misdiagnosis of α-Thalassemia Heterozygotes as Homozygotes Due to Base Mutations in the Primer Binding Region. 引物结合区碱基突变导致α-地中海贫血杂合子误诊为纯合子。

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-06-01 DOI: 10.1080/03630269.2025.2512899

Lihua Ye, Wei Li, Guixi Wei, Xuelian Shen, Shan Ren, Liang Liang, Aiqiong Jiang, Youqiong Li

{"title":"Misdiagnosis of α-Thalassemia Heterozygotes as Homozygotes Due to Base Mutations in the Primer Binding Region.","authors":"Lihua Ye, Wei Li, Guixi Wei, Xuelian Shen, Shan Ren, Liang Liang, Aiqiong Jiang, Youqiong Li","doi":"10.1080/03630269.2025.2512899","DOIUrl":"https://doi.org/10.1080/03630269.2025.2512899","url":null,"abstract":"Misdiagnosis of α-thalassemia genotypes due to primer site mutations presents diagnostic challenges in Chinese populations where -α3.7 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 -α3.7 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.","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"1-7"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heterozygous Beta Thalassemia with Segmental Duplication of chr16p13.3 Leading to Thalassemia Intermedia Phenotype: A Report of 2 Cases with Review of Literature. 杂合型β地中海贫血伴chr16p13.3片段重复导致地中海贫血中间型：附2例报告并文献复习

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-05-01 Epub Date: 2025-04-25 DOI: 10.1080/03630269.2025.2492696

Ekta Jajodia, Neeraj Arora, Moquitul Haque, Tusti Ganguly, Mukesh Kumar, Spandan Chaudhary, Firoz Ahmad, Pooja Chaudhary, Ankit Jitani

{"title":"Heterozygous Beta Thalassemia with Segmental Duplication of chr16p13.3 Leading to Thalassemia Intermedia Phenotype: A Report of 2 Cases with Review of Literature.","authors":"Ekta Jajodia, Neeraj Arora, Moquitul Haque, Tusti Ganguly, Mukesh Kumar, Spandan Chaudhary, Firoz Ahmad, Pooja Chaudhary, Ankit Jitani","doi":"10.1080/03630269.2025.2492696","DOIUrl":"10.1080/03630269.2025.2492696","url":null,"abstract":"Heterozygous β-thalassemia is typically asymptomatic, but when accompanied by α-globin gene multiplication, patients may exhibit clinical symptoms. We present two rare cases of heterozygous β-thalassemia where segmental duplications on chr16p13.3 led to increased α-globin gene copies, resulting in a thalassemia intermedia phenotype. One patient exhibited a novel de-novo duplication spanning 2.57 MB, while the other had a 173.8 KB duplication at the chr16p13.3 locus. These two cases are presented to underscore the significance of thorough and systematic evaluation in diagnosing rare forms of thalassemia accurately. Our study also compiles all reported cases of heterozygous β-thalassemia with large segmental duplications on chr16p13.3, leading to an excess of α-globin genes. A total of ten studies have been published in the literature so far. Importantly, the 2.57 MB segmental duplication identified in our study is a novel variant not previously documented in the literature.","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"222-228"},"PeriodicalIF":1.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatobiliary Manifestations in Thalassemia Patients: A Narrative Review. 地中海贫血患者肝胆表现：叙述性回顾。

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-05-01 Epub Date: 2025-04-28 DOI: 10.1080/03630269.2025.2493946

Asha Tiwari, Ekta Rao, Iswarya Suresh, Manish Tiwari, Ravindra Kumar

引用次数: 0

High Prevalence of Hb Riccarton Challenges HbA1c Analysis in a Danish Clinical Laboratory Using the Tosoh G11. 在丹麦临床实验室使用Tosoh G11进行HbA1c分析时，乙型肝炎的高流行率提出了挑战。

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-05-01 Epub Date: 2025-05-29 DOI: 10.1080/03630269.2025.2509004

Ida Stangerup, Andreas Glenthøj, Nanna Brøns, Majbritt Lund Witte, Ole Birger Pedersen, Christian Erikstrup, Jesper Petersen, Sisse Rye Ostrowski, Thore Hillig

{"title":"High Prevalence of Hb Riccarton Challenges HbA1c Analysis in a Danish Clinical Laboratory Using the Tosoh G11.","authors":"Ida Stangerup, Andreas Glenthøj, Nanna Brøns, Majbritt Lund Witte, Ole Birger Pedersen, Christian Erikstrup, Jesper Petersen, Sisse Rye Ostrowski, Thore Hillig","doi":"10.1080/03630269.2025.2509004","DOIUrl":"10.1080/03630269.2025.2509004","url":null,"abstract":"Ion-exchange high-performance liquid chromatography (HPLC) is commonly used to measure hemoglobin A1c (HbA1c) by distinguishing it from other hemoglobin (Hb) fractions based on net charge. Hb variants can interfere with this analysis, leading to spurious HbA1c results, particularly in HPLC-based methods. This study investigated blood samples showing an HV3 peak - which indicates an Hb variant - on the Tosoh G11 chromatogram during routine HbA1c analysis in a Danish laboratory. Over 30 workdays, 53/33,006 samples displayed an HV3 peak. Sanger sequencing identified Hb Riccarton as the most common variant associated with these peaks (n = 27), consistent with its prevalence in the Danish Blood Donor Study, suggesting it is common in the Danish Caucasian population. Hb Riccarton posed a particular analytical challenge, as over half of the cases showed fluctuating HV3 peaks, initially separated from the HbA1c fraction but subsequently integrated into it upon re-analysis. In regions where Hb Riccarton is prevalent, clinical laboratories using the Tosoh G11 must be aware of this phenomenon to avoid bias and inconsistency in HbA1c reporting. Following Hb Riccarton, HV3 peaks most often indicated HbE heterozygosity (n = 16). Compared to Tosoh G11, HbA1c from the DCA Vantage showed a mean bias of -9.7% for HbE, versus -2.1% in samples without Hb variants. For Hb Riccarton, the bias was -7.2% when the HV3-peak was integrated, and +8.6% when separated from the HbA1c fraction. However, if clinicians are aware of these variants being present, both methods may be used for diabetes monitoring if applied consistently.","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"187-194"},"PeriodicalIF":1.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Estradiol is Pro-Nociceptive and Associated with a Small-Fiber Neuropathy Among Premenopausal Women with Sickle Cell Disease. 雌二醇在绝经前镰状细胞病患者中具有促伤害作用并与小纤维神经病变相关

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-05-01 Epub Date: 2025-04-14 DOI: 10.1080/03630269.2025.2489634

Zachary Ramsay, Deva Sharma, Margaret Wisdom-Phipps, Nicki Chin, Leroy Campbell, Jennifer Knight-Madden, Monika Asnani

{"title":"Estradiol is Pro-Nociceptive and Associated with a Small-Fiber Neuropathy Among Premenopausal Women with Sickle Cell Disease.","authors":"Zachary Ramsay, Deva Sharma, Margaret Wisdom-Phipps, Nicki Chin, Leroy Campbell, Jennifer Knight-Madden, Monika Asnani","doi":"10.1080/03630269.2025.2489634","DOIUrl":"10.1080/03630269.2025.2489634","url":null,"abstract":"Vaso-occlusive crisis (VOC) pain episodes often occur with menses and concurrent hormonal contraceptive use may reduce their frequency. This study tested the hypothesis that among women with sickle cell disease (SCD), sex hormones are associated with pain detection thresholds. Women with SCD aged minimum 18 years with regular menses, and without acute illnesses, pregnancy, oophorectomy, or hormonal contraceptive use within three months prior were included. Pain detection thresholds for heat (HPT) and pressure (PPT), and serum estradiol, progesterone and testosterone were measured at follicular and luteal phases. The Adult Sickle Cell Quality-of-Life Measurement Information System assessed quality-of-life and VOC frequency and severity scores. Generalized linear mixed models were performed, including the day of the cycle standardized by cycle length. Among 125 participants, neither the day nor phase of the menstrual cycle was associated with PPT or HPT. In multivariate analyses, worse VOC scores (β = 1.7) and severe genotype (β = -46.0) were associated with higher and lower trapezius PPT, respectively. Older age was associated with lower forearm HPT (β = -0.1). Among leg measurements, ovulatory cycles (β = -1.1) and hydroxyurea use (β = -1.2) were associated with lower HPT, while worse VOC scores (β = 0.1) were associated with higher HPT. Higher estradiol was associated with lower HPT at the leg (β = -0.02), with an interaction with the cycle day (β = 0.001) predicting lower thresholds earlier in the cycle for the same estradiol level. Estradiol is associated with a time-varying, length-dependent small-fiber neuropathy among SCD women; and may be a potential therapeutic target and biomarker for SCD pain.","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"161-171"},"PeriodicalIF":1.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rare Case of Homozygosity for CYB5R3 Variant c.235C > T p.(Arg79Trp) Causing Type II Methemoglobinemia. 罕见的CYB5R3变异c.235C >tp .（Arg79Trp）引起II型高铁血红蛋白血症的纯合性病例

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-05-01 Epub Date: 2025-05-14 DOI: 10.1080/03630269.2025.2489639

Selma Kofoed Bendtsen, Richard van Wijk, Jesper Brix Petersen, Per Jensen, Jens Helby, Andreas Glenthøj

{"title":"Rare Case of Homozygosity for CYB5R3 Variant c.235C > T p.(Arg79Trp) Causing Type II Methemoglobinemia.","authors":"Selma Kofoed Bendtsen, Richard van Wijk, Jesper Brix Petersen, Per Jensen, Jens Helby, Andreas Glenthøj","doi":"10.1080/03630269.2025.2489639","DOIUrl":"10.1080/03630269.2025.2489639","url":null,"abstract":"Type II methemoglobinemia is a rare genetic condition in which deficiency of the enzyme NADH-cytochrome b5 reductase 3 encoded by the gene CYB5R3 causes neurological symptoms in addition to elevated blood methemoglobin levels. The clinical presentation of Type II methemoglobinemia extends beyond hematological symptoms and include developmental delays, intellectual disability, and severe neurological symptoms. Here we present a case of a young male of Turkish origin diagnosed with type II hereditary methemoglobinemia at age 28. The proband has congenital hearing loss and was diagnosed with infantile autism in adolescence. After several hospital admissions with dyspnea, low oxygen saturation, methemoglobin levels at 4-19%, and normal p50 of 27.0 mmHg, he was evaluated for congenital methemoglobinemia. Genetic testing using targeted next generation sequencing identified the rare pathogenic CYB5R3 c.235C > T p.(Arg79Trp) missense variant (NM_001171660.2, NP_001165131.1). Enzymatic testing of NADH-cytochrome b5 reductase 3 of the patient and the mother showed decreased activities of 0.6 U/g Hb and 6.7 U/g Hb, respectively, compared to a normal group with a mean of 12 U/g Hb (standard deviation 1.7 U/g Hb). The patient had hemoglobin levels within normal and osmotic gradient ektacytometry was performed and found normal. To our knowledge, this constitutes the first report of a CYB5R3 c.235C > T homozygous. This case report emphasizes the importance of considering rare genetic disorders in patients with unexplained neurological and auditory deficits. The patient consented to publication of this case story.","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"218-221"},"PeriodicalIF":1.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of HbH Disease Caused by Compound Heterozygotes α⁺-Thalassemia 3.7 kb Deletion and a Large Novel α⁰-Thalassemia Deletion. 复合杂合子α+-地中海贫血3.7 kb缺失和α0-地中海贫血缺失引起的HbH疾病的特征

IF 1.2 4区医学

Hemoglobin Pub Date : 2025-05-01 Epub Date: 2025-05-05 DOI: 10.1080/03630269.2025.2495698

Chedtapak Ruengdit, Manoo Punyamung, Kritsanee Maneewong, Pinyaphat Khamphikham, Wanicha Tepakhan, Sakorn Pornprasert

{"title":"Characterization of HbH Disease Caused by Compound Heterozygotes α+-Thalassemia 3.7 kb Deletion and a Large Novel α0-Thalassemia Deletion.","authors":"Chedtapak Ruengdit, Manoo Punyamung, Kritsanee Maneewong, Pinyaphat Khamphikham, Wanicha Tepakhan, Sakorn Pornprasert","doi":"10.1080/03630269.2025.2495698","DOIUrl":"10.1080/03630269.2025.2495698","url":null,"abstract":"We characterized here for the first time the deletional HbH disease caused by a large novel α0-thalassemia deletion in a 26-year-old Burmese pregnant woman. Capillary electrophoresis (CE) electropherogram revealed HbA2ABart's H, whereas, a single-tube multiplex real-time PCR with EvaGreen and high-resolution melting (HRM) analysis for diagnosis of three common α0-thalassemia --SEA, --THAI, and --CR deletions showed a negative result. Thus, a multiplex ligation-dependent probe amplification (MLPA) analysis was performed. The α-globin gene cluster deletion was observed spanning from upstream of HBZ to downstream of HBQ1 exon 3 covering three functional genes (HBZ, HBA2, and HBA1). This large novel deletion has not been reported previously thus we named it α0-thalassemia (--BURMESE) due to its origin. In addition, deletional HbH disease is a result of compound heterozygosity for --BURMESE/-α3.7. Therefore, the characterization and identification of --BURMESE is essential for genetic counseling and preventing new cases of HbH disease and Hb Bart's hydrops fetalis.","PeriodicalId":12997,"journal":{"name":"Hemoglobin","volume":" ","pages":"229-232"},"PeriodicalIF":1.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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