Genotyping of BCL11A and HBS1L-MYB SNPs associated with fetal haemoglobin levels: a SNaPshot minisequencing approach

IntroductionDespite being one of the first diseases to be genetically characterised, β-thalassaemia remains a disorder without a cure in a majority of patients. Most patients with β-thalassaemia receive only supportive treatment and therefore have a poor quality of life and shorter life spans. Hydroxyurea, which has shown to induce fetal haemoglobin synthesis in human erythroid cells, is currently recommended for the treatment of sickle cell disease. However, its clinical usefulness in transfusion-dependent β-thalassaemia is unclear. Here, we present a protocol for a randomised double-blind controlled clinical trial to evaluate the efficacy and safety of oral hydroxyurea in transfusion-dependent β-thalassaemia.Methods and analysisThis single-centre randomised double-blind placebo-controlled clinical trial is conducted at the Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Adult and adolescent patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into the intervention or control group. The intervention group receives oral hydroxyurea 10–20 mg/kg daily for 6 months, while the control group receives a placebo which is identical in size, shape and colour to hydroxyurea without its active ingredient. Transfused blood volume, pretransfusion haemoglobin level, fetal haemoglobin percentage and adverse effects of treatment are monitored during treatment and 6 months post-treatment. Cessation or reduction of blood transfusions during the treatment period will be the primary outcome measure. The statistical analysis will be based on intention to treat.Ethics and disseminationEthical approval has been obtained from the Ethics Committee of Faculty of Medicine, University of Kelaniya (P/116/05/2018) and the trial is approved by the National Medicinal Regulatory Authority of Sri Lanka. Results of the trial will be disseminated in scientific publications in reputed journals.Trial registration numberSLCTR/2018/024; Pre-results.

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Adult and fetal haemoglobin J-Sardegna [α50(CE8)His→Asp]: functional and molecular modelling studies

Biochemical Journal ◽

10.1042/bj3460193 ◽

2000 ◽

Vol 346 (1) ◽

pp. 193-199 ◽

Cited By ~ 3

Author(s):

Marcella CORDA ◽

Maria C. DE ROSA ◽

Maria G. PELLEGRINI ◽

Maria T. SANNA ◽

Alessandra OLIANAS ◽

...

Keyword(s):

Functional Properties ◽

Computational Modelling ◽

Oxygen Affinity ◽

Oxygen Binding ◽

Structural Level ◽

Fetal Haemoglobin ◽

Significant Difference ◽

Molecular Modelling Studies ◽

Modelling Studies ◽

2,3 Dpg

Haemoglobin (Hb) J-Sardegna [α50(CE8)His → Asp] is a haemoglobin variant characteristic of subjects from the island of Sardinia. Here we report a study of the functional properties of both fetal and adult Hb J-Sardegna. The results indicate that adult Hb J-Sardegna displays an oxygen affinity that is higher than that of adult Hb only in the presence of 2,3-diphosphoglycerate (2,3-DPG). On the contrary, at 20 °C, the oxygen affinity of fetal Hb J-Sardegna is identical to that of normal fetal haemoglobin, both in the presence and in the absence of 2,3-DPG. A significant difference between these two systems (i.e. a higher oxygen affinity of fetal Hb J-Sardegna) shows up very clearly only when temperature is increased to 37 °C. Hence in fetal Hb, the main effect of the amino acid substitution is a decrease in the overall enthalpy change of oxygenation. The results outline the role of the α1-β1 interface in assessing the thermodynamics of oxygen binding. The functional properties of both adult and fetal Hb J-Sardegna have been interpreted at the structural level in light of the results obtained by a computational modelling approach performed in comparison with HbA and Hb Aichi, a variant characterized by a different mutation [α50(CE8)His → Arg] at the same position.

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Quantification of feto-maternal haemorrhage (FMH) by flow cytometry: anti-fetal haemoglobin labelling potentially underestimates massive FMH in comparison to labelling with anti-D

Transfusion Medicine ◽

10.1046/j.1365-3148.2003.00416.x ◽

2003 ◽

Vol 13 (1) ◽

pp. 25-34 ◽

Cited By ~ 20

Author(s):

G. A. Kennedy ◽

R. Shaw ◽

S. Just ◽

G. Bryson ◽

F. Battistutta ◽

...

Keyword(s):

Flow Cytometry ◽

Fetal Haemoglobin

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Effects of fetal haemoglobin on systemic oxygenation in preterm infants and the development of retinopathy of prematurity PacIFiHER Report No. 2

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319546 ◽

2021 ◽

pp. bjophthalmol-2021-319546

Author(s):

Kim Jiramongkolchai ◽

Michael X Repka ◽

Jing Tian ◽

Sue W Aucott ◽

Jennifer Shepard ◽

...

Keyword(s):

Intensive Care Unit ◽

Preterm Infants ◽

Retinopathy Of Prematurity ◽

Neonatal Intensive Care ◽

Blood Gas ◽

Dissociation Curve ◽

Fetal Haemoglobin ◽

Oxyhaemoglobin Dissociation Curve ◽

Increased Risk ◽

Oxygenation Indices

Background/aimsFetal haemoglobin (HbF) has an oxyhaemoglobin dissociation curve that may affect systemic oxygenation and the development of retinopathy of prematurity (ROP). The study aim is to characterise the effects of HbF levels on systemic oxygenation and ROP development.MethodsProspective study conducted from 1 September 2017 through 31 December 2018 at the Johns Hopkins NICU. Preterm infants with HbF measured at birth, 31, 34 and 37 weeks post-menstrual age (PMA), complete blood gas and SpO2 recorded up to 42 weeks PMA, and at least one ROP exam were included.ResultsSixty-four preterm infants were enrolled. Higher HbF was associated with significantly higher SpO2, lower PCO2, lower FiO2 from birth to 31 weeks PMA and 31 to 34 weeks PMA (rs=0.51, rs=−0.62 and rs=−0.63; p<0.0001 and rs=0.71, rs=−0.58 and rs=−0.79; p<0.0001, respectively). To maintain oxygen saturation goals set by the neonatal intensive care unit, higher median FiO2 was required for HbF in the lowest tercile from birth compared with HbF in the highest tercile to 31 weeks and 31 to 34 weeks PMA; FiO2=35 (21–100) versus 21 (21–30) p<0.006 and FiO2=30 (28–100) versus 21 (21–30) p<0.001, respectively. Preterm infants with ROP had poorer indices of systemic oxygenation, as measured by median levels of SpO2 and PCO2, and lower levels of HbF (p<0.039 and p<0.0001, respectively) up to 34 weeks PMA.ConclusionLow HbF levels correlated with poor oxygenation indices and increased risk for ROP. O2 saturation goals to prevent ROP may need to incorporate relative amount of HbF.

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Screening for Sickle Cell Disease: A Hospital Based Study in Eastern Odisha, India

South Asian Journal of Experimental Biology ◽

10.38150/sajeb.2(2).p57-60 ◽

2012 ◽

Vol 2 (2) ◽

pp. 57-60

Author(s):

Jayanti Mishra ◽

Sanghamitra Pati ◽

Mohammad Akhtar Hussain ◽

Niraj Srivastava ◽

Sindhubala Mishra

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Trait ◽

Cell Disease ◽

Medicine Department ◽

Fetal Haemoglobin ◽

Medical College ◽

Rbc Indices ◽

And Gender ◽

Cell Gene

The highest frequency of sickle cell gene in India is reported in Odisha. The present study was taken up to assess the presence of sickle cell disease among febrile patients of a medical college of eastern Odisha. Patients referred from both pediatric and medicine department to the Hematology section of the department of Pathology, SCB Medical College, Cuttack were subjected to measurement of RBC indices, Sickling test, Haemoglobin Electrophoresis and Fetal Haemoglobin Estimation. Out of total 1000 referred patients 76(7.6%) were found to be positive for sickling. Twoâ€third of sicklingpositive patients had sickle cell trait with electrophoretic AS band. There was a significant association between age and positive sickling (χ2 = 24.357; df = 4, P = <0.0001). No significant association was observed between sickling and gender. Sickle cell positive cases are not uncommon in eastern Odisha. Our study demonstrated sickle cell trait to be more common among screened patients than other forms of sickle cell diseases.

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