Hemoglobin G Makassar: β6 Glu→Ala

Blackwell, R. Q.; Oemijati, S; Pribadi, Wita; Weng, M.-I.; Liu, C.-S.

doi:10.1016/0005-2795(70)90297-7

Cited by 46 publications

(9 citation statements)

References 16 publications

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“…Our findings are in accordance with other studies on the benign state of Hb G‐Makassar [1–4]. The anaemia in two hospitalised cases in our study was secondary to an identified co‐morbidity which was resolved after specific treatment.…”

Section: Discussionsupporting

confidence: 93%

“…Hb G‐Makassar is considered a benign Hb variant. The patients may present with no symptom or mild anaemia, be it for those with Hb G‐Makassar heterozygote (NG_000007.3:g.[70614A > C];[70614A =]) or homozygote (NG_000007.3:g.[70614A > C];[70614A > C]); or those with a compound Hb G‐Makassar/β‐globin variant [1–6]. In contrast, Hb S has a spectrum of clinical presentation according to the interaction of the variant with different genotypes in HBB allele.…”

Section: Introductionmentioning

confidence: 99%

“…Haemoglobin (Hb) G-Makassar (NG_000007.3:g.[70614A > C]) is a rare β-chain variant in Southeast Asia. It was named after a city in Sulawesi, Indonesia, called Makassar, where it was first discovered in 1969 [1]. The following incidence was then identified in Thailand, Malaysia and the United Kingdom, but higher incidence was observed in Southeast Asia than in Europe [2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Esa,

Mohamad,

Hamzah

et al. 2023

eJHaem

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“…However, this SNP can be converted with ABE to a G C G (Ala) through A•T-to-G•C conversion on the opposite strand ( Fig. 6a ) to yield the HBB E6A genotype, known as the Makassar allele ( HbG ), which is thought to be non-pathogenic in both homozygous and heterozygous individuals 47 – 49 . Unfortunately, the only NGG or NGN PAMs available at this site place the target A at either protospacer position 2 or 9, respectively, outside the editing window for ABE 12 .…”

Section: Resultsmentioning

confidence: 99%

Continuous evolution of SpCas9 variants compatible with non-G PAMs

et al. 2020

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The targeting scope of Streptococcus pyogenes Cas9 (SpCas9) and its engineered variants is largely restricted to protospacer-adjacent motif (PAM) sequences containing Gs. Here, we report the evolution of three new SpCas9 variants that collectively recognize NRNH PAMs (where R = A or G and H = A, C, or T) using phage-assisted non-continuous evolution (PANCE), three new phage-assisted continuous evolution (PACE) strategies for DNA binding, and a secondary selection for DNA cleavage. The targeting capabilities of these evolved variants and SpCas9-NG were characterized in HEK293T cells using a library of 11,776 genomically integrated protospacer-sgRNA pairs containing all possible NNNN PAMs. The evolved variants mediate indel formation and base editing in human cells and enable the A•T-to-G•C base editing of a sickle-cell anemia mutation using a previously inaccessible CACC PAM. These new evolved SpCas9s, together with previously reported variants, in principle enable targeting the majority of NR PAM sequences and substantially reduce the fraction of genomic sites that are inaccessible by Cas9-based methods.

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“…There are no natural hemoglobin variants with Leu, Ile, Phe, or Trp at the β-6 residue. Hb G-Makassar with Glu6Ala mutation in the β chain, albeit rare, is the only natural variant with a hydrophobic β-6 residue other than HbS. − In compound heterozygotes Hb G-Makassar/β 0 -thalassemia (no production of hemoglobin β chains) and Hb G-Makassar/HbE, there have been reports of anemia. , Indications of thalassemia were found, but no sickle cells were observed in the peripheral blood film of a compound heterozygous patient for Hb G-Makassar/HbE . Heterozygous HbA/Hb E individuals are known to be asymptomatic; since the patient showed signs of thalassemia, the Hb G-Makassar mutation did have a detrimental effect.…”

Section: Results and Discussionmentioning

confidence: 99%

Molecular Dynamics of Hemoglobin Reveals Structural Alterations and Explains the Interactions Driving Sickle Cell Fibrillation

Maity

Pal

2021

J. Phys. Chem. B

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In sickle cell anemia, deoxyhemoglobin deforms RBCs by forming fibrils inside that disintegrate on oxygenation. We studied 100 ns long all-atom molecular dynamics (MD) for sickle and normal hemoglobin fibril models to understand this process, complemented by multiple 1 μs MD for a single tetramer of sickle and normal hemoglobin in deoxy and oxy states. We find that the presence of hydrophobic residues without a bulky side chain at β-6 in hemoglobin is the reason for the stability of the fibrils. Moreover, the free energy landscapes from MD of hemoglobin starting in the tensed (T) state capture the putative transition from T to relaxed (R) state, associated with oxygen binding. The three conformational wells in the landscapes are characterized by the quaternary changes where one αβ dimer rotates with respect to the other. The conformational changes from the oxygenation of sickle hemoglobin hinder the intermolecular contacts necessary for fibril formation.

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Hemoglobin G Makassar: β6 Glu→Ala

Cited by 46 publications

References 16 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

Continuous evolution of SpCas9 variants compatible with non-G PAMs

Molecular Dynamics of Hemoglobin Reveals Structural Alterations and Explains the Interactions Driving Sickle Cell Fibrillation

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