IthaID: 529



Names and Sequences

Functionality: Globin gene causative mutation
Common Name: CD 43 TTC>TTG [Phe>Leu] HGVS Name: HBA2:c.132C>G
Hb Name: Hb Hirosaki Protein Info: α2 43(CE1) Phe>Leu

Context nucleotide sequence:
CCTTCCCCACCACCAAGACCTACTT [C/G] CCGCACTTCGACCTGAGCCACGGCT (Strand: +)

Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYLPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR

Comments: The phenylalanyl side chain at the position α43 (CE1) is in close contact with the heme moiety on the side of the distal histine in helix E7. Altered heme pocket. Phe>Leu replacement changes the hydrophobic heme to the hydrophilic state, resulting in heme oxygenation and leading to the formation of an unstable haemoglobin (Hb). Extremely unstable and rapidly degraded after biosynthesis, hence not detected during routine screening. Positive heat precipitation and isopropanol tests. Presence of Heinz bodies. Initially reported in a family with congenital nonspherocytic hemolytic disease, later in additional families and as a sporadic case. Affected individuals were in heterozygous state. Autosomal dominant mode of inheritance. Differences in the clinical severity of the affected individuals, ranging from asymptomatic presentation (hypochromic and normocytic anaemia) to repeated hemolytic crises. Ameliorated after splenectomy. Also reported as a severe fetal anaemia with hydrops fetalis due to the co-inheritance of Hb Hirosaki with an α0-thalassaemia mutation (--SEA).

Location

Chromosome: 16
Locus: NG_000006.1
Locus Location: 34024
Size: 1 bp
Located at: α2
Specific Location: Exon 2

Phenotype

Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: α-chain variant
Allele Phenotype:Dominant
Stability: Hyperunstable
Oxygen Affinity: N/A
Associated Phenotypes: Haemolytic anaemia [HP:0001878]

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: Missense codons (Protein Structure)
Ethnic Origin: Japanese, Chinese
Inheritance: Dominant
DNA Sequence Determined: Yes
Detection Methods: Direct DNA sequencing

Sequence Viewer

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Publications / Origin

  1. Ohba Y, Miyaji T, Matsuoka M, Yokoyama M, Numakura H, Hemoglobin Hirosaki (alpha 43 [CE 1] Phe replaced by Leu), a new unstable variant., Biochim. Biophys. Acta , 405(1), 155-60, 1975 PubMed
  2. Ohba Y, Miyaji T, Matsuoka M, Yokoyama M, Further studies on hemoglobin Hirosaki: demonstration of its presence at low concentration., Hemoglobin , 2(3), 281-6, 1978 PubMed
  3. Yokoyama M, Kudo Y, Sato Y, Izumi Y, Ohba Y, Miyaji T, Clinical features and biochemical aspects of red blood cells in Hb Hirosaki., Tohoku J. Exp. Med., 133(2), 187-96, 1981 PubMed
  4. Ohba Y, Yamamoto K, Hattori Y, Yamamoto K, Miyaji T, Shiosaki F, Mori H, Yamaguchi K, Takahashi M, Mizoguchi H, Further cases of Hb Hirosaki in two Japanese families., Int. J. Hematol. , 54(1), 15-23, 1991 PubMed
  5. Tanaka Y, Matsui K, Matsuda K, Shinohara K, Haranob K, A family with hemoglobin Hirosaki., Int. J. Hematol., 82(2), 124-6, 2005 PubMed
  6. Li Q, Li Y, Zhong M, Zhang VW, Jin W, Li S, Li L, A Rare Hb H Hydrops Fetalis Syndrome Caused by the - - Deletion in Combination with the Rare Hb Hirosaki Mutation in a Chinese Patient., Hemoglobin, 42(4), 278-280, 2018 PubMed
  7. Takahata M, Ibata M, Hirano T, Iwasaki H, [Hb Hirosaki hemoglobinopathy initially suspected due to low oxygen saturation levels and abnormally low HbA1c levels]., Rinsho Ketsueki, 60(3), 213-217, 2019 PubMed
Created on 2010-06-16 16:13:15, Last reviewed on 2019-06-24 12:01:21 (Show full history)

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