Investigation of correlation between H63D and C282Y mutations in HFE gene and serum Ferritin level in beta-thalassemia major patients

Rahmani, Romina; Naseri, Parisa; Safaroghli‐Azar, Ava; Tarighi, Shahriar; Hosseini, Tahereh; Hojjati, Mohammad Taher

doi:10.1016/j.tracli.2019.05.003

Cited by 7 publications

(3 citation statements)

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“…Romina Rahmani et al described a significant rise in serum ferritin among TDT patients H63D and C282Y pathogenic variants [ 29 ]. Zekavat OR et al described a significant rise in serum ferritin without an increase in hepatic and cardiac IO in a study among TDT patients with H63D pathogenic variant.…”

Section: Discussionmentioning

confidence: 99%

Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes

et al. 2022

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Background Iron overload (IO) is a complication in transfusion dependent beta thalassaemia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka. Materials and Methods Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for a period of one year in all. Those who were ≥ 8 years of age (40 patients) underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes. Results The median age of the patients of this cohort was 10 years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The median level of serum ferritin was 2452 ng/dl. Hepatic IO was seen in 37 (92.5%) patients and cardiac IO was seen in 17 (42.5%) patients. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO. Thirty-two (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. Eight (15.4%) and 1 (1.9%) patients were heterozygotes for pathogenic and likely pathogenic variants of HFE genes respectively. There were no pathogenic variants for the TfR2 and SLC40A1 genes. The heterozygotes of the pathogenic variants of the HFE were not at increased risk of IO. Conclusions Cardiac T2* MRI helps to detect cardiac IO in asymptomatic patients. It is important to perform hepatic and cardiac T2* MRI to detect IO in patients with TDT. There was no statistically significant correlation between pathogenic variants of HBB and HFE genes with hepatic and cardiac IO in this cohort of patients.

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Section: Discussionmentioning

confidence: 99%

Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes

et al. 2022

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“…Romina Rahmani et al described a signi cant rise in serum ferritin among TDT patients H63D and C282Y pathogenic variants 21 . Zekavat OR et al described a signi cant rise in serum ferritin without an increase in hepatic and cardiac IO in a study among TDT patients with H63D pathogenic variant.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Iron Overload in a Cohort of Sri Lankan Patients with Transfusion Dependent Beta Thalassaemia and its Correlation with Pathogenic Variants in HBB, HFE, SLC40A1, and TFR2 Genes

Dissanayake

Samarasinghe

Waidyanatha

et al. 2021

Preprint

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Background. Iron overload (IO) is a complication in transfusion dependent beta thalassaemmia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.Materials and Methods. Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for one year in all. Those who were ≥ 8 years of age underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes.Results. The mean age (SD) of this cohort was 9.5 (±4.6) years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The mean serum ferritin was 3405 (±2670.5) ng/dl. Hepatic IO was seen in 38 (95%) patients and cardiac IO was seen in 17 (42.5%) patients. All patients with cardiac IO were asymptomatic and had normal echocardiogrammes. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO.32 (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. 9 (17.3%) and 3 (5.8%) patients were heterozygotes for pathogenic variants of HFE and SLC40A1 genes respectively. There were no pathogenic variants for the TfR2 gene. The heterozygotes of the pathogenic variants of the HFE and SLC40A1 genes were not at increased risk of IO.Conclusions. Cardiac T2* MRI helps to detect cardiac IO prior to the onset of symptoms when the echocardiogramme is normal. It is important to perform hepatic and cardiac MRI T2* to detect IO in patients with TDT.

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“…4 Intestinal iron absorption is also increased in thalassemia-major due to the hepcidin suppression by twisted gastrulation protein homolog-1 (TWSG1) and growth differentiation factor-15 (GDF-15), released from erythroblasts during ineffective erythropoiesis. 5 This excess iron amasses in tissues, especially the liver, heart and endocrine organs. 6 Growth retardation, hypogonadism, hypoparathyroidism, hypothyroidism and glycaemic abnormalities are the major endocrine complications reported in iron-overloaded patients of BTM.…”

Section: Introductionmentioning

confidence: 99%

Spectrum of HBB gene variants and major endocrine complications in thalassemia patients of Pakistan

Muhammad Bilal Ghafoor,

Ikram Din Ujjan,

Ali Muhammad Waryah

et al. 2023

J Pak Med Assoc

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Objectives: To determine the molecular characterisation of beta-thalassemia major patients, pattern of major endocrine complications and its association with haemoglobin subunit beta gene variants. Method: The cross-sectional study was conducted from November 2021 to November 2022 after approval from the ethics review committee of Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, and comprised of 88 patients with beta thalassemia major aged >8 years and having serum ferritin level >1000µg/L. The subjects were analysed for haemoglobin subunit beta gene variants and major endocrine complications, like growth retardation, hypogonadism, hypothyroidism, hypoparathyroidism and diabetic abnormalities using an automatic chemistry analyser, fully automatic chemiluminescence immunoassay analyser, enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Data was analysed using SPSS 25. Results: Of the 88 subjects, 40(45.4%) were girls and 48(54.5%) were boys. The overall mean age was 12±2.81 years. Of the total, 55(62.5%) had growth retardation, 41(46.6%) were cases of hypogonadism, 16(18.1%) hypothyroidism, 5(5.7%) hypoparathyroidism, 3(3.4%) diabetes mellitus and 8 (9.1%) had impaired glucose tolerance. Also, 65(73.9%) patients confronted at least one endocrine complication. Endocrine complications were strongly associated with serum ferritin levels (p=0.000). The most common haemoglobin subunit beta gene variant identified was IVSI-5 (G>C) in 36(40.9%), and the least identified variant was cluster of differenctiation-26 (G>A) 1(1.1%). The association between haemoglobin subunit beta gene variants with endocrine complications was statistically non-significant (p>0.05). Conclusion: IVSI-5 (G>C) was found to be the most frequent haemoglobin subunit beta gene variant among beta-thalassemia major patients. Key Words: Beta-thalassemia major, Endocrine complications, Growth retardation, Hypothyroidism, Parathyroidism, Diabetes mellitus.

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Investigation of correlation between H63D and C282Y mutations in HFE gene and serum Ferritin level in beta-thalassemia major patients

Cited by 7 publications

References 16 publications

Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes

Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes

Assessment of Iron Overload in a Cohort of Sri Lankan Patients with Transfusion Dependent Beta Thalassaemia and its Correlation with Pathogenic Variants in HBB, HFE, SLC40A1, and TFR2 Genes

Spectrum of HBB gene variants and major endocrine complications in thalassemia patients of Pakistan

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