IthaID: 698



Names and Sequences

Functionality: Globin gene causative mutation
Common Name: CD 103 CAC>CGC [His>Arg] HGVS Name: HBA1:c.311A>G | HBA2:c.311A>G
Hb Name: Hb Contaldo Protein Info: α2 or α1 103(G10) His>Arg

Context nucleotide sequence:
CTCTTCTCTGCACAGCTCCTAAGCC [A/G/T] CTGCCTGCTGGTGACCCTGGCCGCC (Strand: +)

Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSRCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR

Comments: Replacement of histidine residue at position α103 in the G helix (G10) by a charged arginine residue, which disrturbs contact with the β chain residue Asn 108 (G10) across the α1β1 interface. Interference with α1β1 dimerization results in the accumulation of free globin subunits. It also destabilizes free α chains by disrupting binding to the chaperone AHSP. Unstable in isopropanol and heat denaturation tests. Discovered as a de novo mutation in a heterozygous proband from North Italy with moderate hemolytic anaemia (severe microcytosis and hypochromia, anisocytosis, isochromic and polychromatic cells, poikilocytosis, and Heinz bodies). The haematological abnormalities could be accentuated by the presence of an additionnal α-thalassemia variant (inferred, not confirmed).

Location

Chromosome: 16
Locus: NG_000006.1
Locus Location: 34345 or 38156
Size: 1 bp or 1 bp
Located at: α1 or α2
Specific Location: Exon 3

Phenotype

Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: α-chain variant
Allele Phenotype:N/A
Stability: Unstable
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: Italian
Inheritance: Recessive
DNA Sequence Determined: No
Detection Methods: Direct DNA sequencing

Sequence Viewer

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Publications / Origin

  1. Sciarratta GV, Ivaldi G, Molaro GL, Sansone G, Salkie ML, Wilson JB, Reese AL, Huisman TH, The characterization of hemoglobin Manitoba or alpha (2)102(G9)Ser----Arg beta 2 and hemoglobin Contaldo or alpha (2)103(G10)His----Arg beta 2 by high performance liquid chromatography., Hemoglobin , 8(2), 169-81, 1984 PubMed
  2. Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013 PubMed
Created on 2010-06-16 16:13:16, Last reviewed on 2019-06-20 14:53:24 (Show full history)

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