Prenatal Diagnosis of the Hemoglobinopathies

Old, John; Traeger-Synodinos, J

doi:10.1002/9781119676980.ch27

Cited by 3 publications

(4 citation statements)

References 117 publications

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“…Similar observation is found in heterozygous Hb S with/without co-inheritance of alpha thalassaemia. It is believed that the elevation of the Hb A 2 value occurs when the affinity of β S -chain towards α-chain is reduced; therefore, more α-chains are available to combine with δ-chains forming Hb A 2 [26]. The same concept was applied to Hb G-Makassar.…”

Section: Discussionmentioning

confidence: 99%

Clinical and haematological characteristics of 38 individuals with Hb G‐Makassar in Malaysia

Esa,

Mohamad,

Hamzah

et al. 2023

eJHaem

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Haemoglobin (Hb) G‐Makassar is a rare Hb variant. It presents a diagnostic challenge as it imitates sickle Hb (Hb S) in standard electrophoresis and high‐performance liquid chromatography assays requiring DNA analysis to confirm diagnosis. Both have point mutations in codon 6, exon 1 in the β‐globin (HBB) gene with different pathogenicities. This study describes the clinical phenotype, haematology and genotype of Hb G‐Makassar. Clinical and laboratory data of 38 cases of Hb G‐Makassar over 8 years were analysed. Hb G‐Makassar was confirmed by a direct sequencing of HBB gene and co‐inheritance of α‐thalassaemia determined through multiplex gap‐PCR and multiplex Amplification Refractory Mutation System polymerase chain reaction. All cases were Malays, predominantly from Terengganu (n = 20, 52.6%). There were 14 (36.8%) males and 24 (63.2%) females with median age of 25 years. Majority (n = 33, 86.8%) had features of thalassaemia trait with mean ± SD for Hb, mean cell volume (MCV) and mean cell haemoglobin (MCH) as 13.21 g/dL ± 1.69, 73.06 ± 4.48 fL and 24.71 ± 1.82 pg, respectively. None had evidence of haemolysis or thromboembolic complications. Six genotypes were identified; ßG‐Makassar/ß,αα/αα (n = 19, 50.0%), ßG‐Makassar/ßE,αα/αα (n = 4, 10.5%), ßG‐Makassar/ßNewYork,αα/αα (n = 1, 2.6%), ßG‐Makassar/ß,αα/‐α (n = 11, 28.9%), ßG‐Makassar/ß,αα/αAdanaα (n = 2, 5.3%) and ßG‐Makassar/ß,αα/–SEA (n = 1, 2.6%). The ßG‐Makassar/ß,αα/αα showed that features of thalassaemia trait with mean ± SD for Hb, MCV and MCH were 13.74 g/dL ± 2.40, 76.18 ± 6.02 fL and 25.79 ± 2.41 pg, respectively. This is the largest study reporting a significant number of Hb G‐Makassar in Malaysia. Although the mutation is similar to Hb S, the phenotype is benign.

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Section: Discussionmentioning

confidence: 99%

Clinical and haematological characteristics of 38 individuals with Hb G‐Makassar in Malaysia

Esa,

Mohamad,

Hamzah

et al. 2023

eJHaem

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“…Informed written consent was obtained from parents/guardians and patients. The diagnosis of BTM was made following international guidelines through complete blood count, including peripheral blood smear morphology, hemoglobin electrophoresis, and PRCs transfusion dependency 41,42. DNA analysis for β-globin mutations was also performed as per the study requirement.…”

Section: Methodsmentioning

confidence: 99%

“…The diagnosis of BTM was made following international guidelines through complete blood count, including peripheral blood smear morphology, hemoglobin electrophoresis, and PRCs transfusion dependency. 41,42 DNA analysis for β-globin mutations was also performed as per the study requirement. The patients' records show that they were given a mean dose of 16 mg/kg/d of HU with an initial starting dose of 10 mg/kg/d.…”

Section: Study Populationmentioning

confidence: 99%

A Pragmatic Scoring Tool to Predict Hydroxyurea Response Among β-Thalassemia Major Patients in Pakistan

Ansari

Hussain

Zohaib

et al. 2021

Journal of Pediatric Hematology/Oncology

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Despite high prevalence and incidence of β-thalassemia in Pakistan, there is very limited work on the use of hydroxyurea (HU) in thalassemia patients in the country. This is the first insight regarding genetic profiling of BCL11A and HU responses in Pakistani β-thalassemia. It correlates single-nucleotide polymorphisms on BCL11A (rs4671393, rs766432) and HBG2 (XmnI), age at first transfusion, and β-globin mutations with HU response in β-thalassemia major (BTM). Of 272 patients treated with HU, 98 were complete responders, 55 partial responders, and 119 nonresponders. Our analysis shows that HU response was significantly associated with patients having IVSI-1 or CD 30 mutation (P < 0.001), age at first transfusion > 1 year (P < 0.001), and with the presence of XmnI polymorphism (P < 0.001). The single-nucleotide polymorphisms of BCL11A were more prevalent among responders, but could not show significant association with HU response (P > 0.05). Cumulative effect of all 5 predicting factors through simple binary scoring indicates that the likelihood of HU response increases with the number of primary and secondary genetic modifiers (P < 0.001). Predictors scoring is a pragmatic tool to foresee HU response in patients with BTM. The authors recommend a score of ≥ 2 for starting HU therapy in Pakistani patients with BTM.

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“…Demographic information and an EDTA/DBS blood sample from one or both parents are required with that of the newborn to help guide the sequence of confirmatory diagnostic tests for specific thalassaemias. Methods of gene-typing for thalassemia based on PCR techniques are as follows: dot-blot analysis, reverse dot-blot analysis, the amplification refractory mutation system, denaturing gradient gel electrophoresis, mutagenically separated polymerase chain reaction, gap-PCR, restriction endonuclease analysis, real-time polymerase chain reaction, Sanger sequencing, pyrosequencing, multiplex ligation-dependent probe amplification and gene array [26][27][28][29] Gap-PCR is used to test for common α-thalassaemia deletions or duplications, as well as all forms of HPFH and Hb Lepore deletions. will identify point mutations in the γ-, α-and β-globin genes are usually captured in direct DNA sequencing but mutations within the alleles as well as large deletions are often missed out.…”

Section: Confirmatory Diagnostic Testing For the Thalassaemiasmentioning

confidence: 99%

Newborn Screening and Thalassaemia Syndrome

Iheanacho¹,

Okeke²

2023

Thalassemia Syndromes - New Insights and Transfusion Modalities

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Haemoglobin variants or haemoglobin disorders are a group of clinical disorders characterised by impairment of synthesis of normal adult haemoglobin, due to genetically determined abnormality in the formation of the globin moiety of the molecule. These disorders fall into two broad groups, that is qualitative (haemoglobinopathies) and quantitative (thalassaemias). In the anthropoids, the most common congenital single-gene disorder is the alteration of the globin genes which account for about 270 million carriers globally. These globin gene alterations cause low/no globin expression (thalassaemia) or abnormal globin protein production (haemoglobinopathy). The clinical manifestation of haemoglobin disorder is the culminated measure of one’s genetic and molecular makeup. Summarily, the study, diagnosis and management of thalassaemia are models of biological principles of human disease. Newborn screening, however, is a system that aims at improving management and/or eradication of genetic disorders from the neonatal stage of life. This chapter will be dealing with the definition and steps involved in newborn screening for thalassaemia.

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Prenatal Diagnosis of the Hemoglobinopathies

Cited by 3 publications

References 117 publications

Clinical and haematological characteristics of 38 individuals with Hb G‐Makassar in Malaysia

Clinical and haematological characteristics of 38 individuals with Hb G‐Makassar in Malaysia

A Pragmatic Scoring Tool to Predict Hydroxyurea Response Among β-Thalassemia Major Patients in Pakistan

Newborn Screening and Thalassaemia Syndrome

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