IthaID: 481



Names and Sequences

Functionality: Globin gene causative mutation Pathogenicity: N/A
Common Name: CD 21 GCT>CCT [Ala>Pro] HGVS Name: HBA2:c.64G>C
Hb Name: Hb Fontainebleau Protein Info: α2 21(B2) Ala>Pro

Context nucleotide sequence:
CGCCTGGGGTAAGGTCGGCGCGCAC [G/C] CTGGCGAGTATGGTGCGGAGGCCCT (Strand: +)

Protein sequence:
MVLSPADKTNVKAAWGKVGAHPGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR

Also known as:

Comments: This variant is a substitution of a propyl residue (α2 Ala21Pro) at the beginning of the B helix. It is an electrophoretically silent variant detected by IEF (migrates as HbA1c) and ion exchange chromatography (HPLC). The variant globin chain can be detected by ESI/MS, but not RP-HPLC. It did not affect the affinity of haemoglobin (Hb) for oxygen. While one paper reported normal Hb stability by isopropanol and heat stability tests [PMID: 2599878], another reported isopropanol precipitation at 25 minutes [PMID: 19657841]. The variant was associated with normal haematological parameters in the heterozygous state. The variant is located in close proximity to the axial interaction interface of the HbS fiber (α2His20-β1Glu22; α1Pro114- α1Ala115-α2Lys16-α2Glu116) [PMID: 26187468]. Co-inheritance with the sickle mutation was reported in a newborn with anaemia at birth, while no follow up data was available.

Phenotype

Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: α-chain variant
Allele Phenotype:N/A
Stability: N/A
Oxygen Affinity: N/A
Associated Phenotypes: N/A

Location

Chromosome: 16
Locus: NG_000006.1
Locus Location: 33839
Size: 1 bp
Located at: α2
Specific Location: Exon 1

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: Missense codons (Protein Structure)
Ethnic Origin: Italian, Iraqi, Omani, Indian, Turkish, UAE
Molecular mechanism: Altered secondary structure
Inheritance: Recessive
DNA Sequence Determined: Yes

Sequence Viewer

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Publications / Origin

  1. Wajcman H, Blouquit Y, Gombaud-Saintonge G, Riou J, Galacteros F, Hb Fontainebleau [alpha 21(B2)Ala----pro], a new silent mutant hemoglobin., Hemoglobin , 13(5), 421-8, 1989 PubMed
  2. Brennan SO, Chan T, Ryken S, Ruskova A, A second case of Hb Fontainebleau [alpha21(B2)Ala-->Pro] in an individual with microcytosis., Hemoglobin, 33(3), 258-61, 2009 PubMed
  3. Upadhye DS, Jain D, Nair SB, Nadkarni AH, Ghosh K, Colah RB, First case of Hb Fontainebleau with sickle haemoglobin and other non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders., J Clin Pathol, 65(7), 654-9, 2012 PubMed
  4. Mashon RS, Nair S, Sawant P, Colah RB, Ghosh K, Das S, Hemoglobin Fontainebleau [a21(B2)Ala>Pro]: The second report from India., Indian J Hum Genet, 19(3), 352-4, 2013 PubMed
  5. Turner A, Sasse J, Varadi A, Hb Fontainebleau (HBA2: c.64G > C) in the United Arab Emirates., Hemoglobin, 38(3), 216-20, 2014 PubMed
  6. Rodríguez-Capote K, Estey MP, Barakauskas V, Bordeleau P, Christensen CL, Zuberbuhler P, Higgins TN, A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy., Clin Biochem, 48(0), 904-7, 2015 PubMed
  7. Henderson SJ, Timbs AT, McCarthy J, Gallienne AE, Proven M, Rugless MJ, Lopez H, Eglinton J, Dziedzic D, Beardsall M, Khalil MS, Old JM, Ten Years of Routine α- and β-Globin Gene Sequencing in UK Hemoglobinopathy Referrals Reveals 60 Novel Mutations., Hemoglobin , 40(2), 75-84, 2016 PubMed
  8. Canatan D, Bilgen T, Çiftçi V, Yazıcı G, Delibaş S, Keser İ, First Observation of Hemoglobin G-Waimanalo and Hemoglobin Fontainebleau Cases in the Turkish Population., Turk J Haematol, 33(1), 71-2, 2016 PubMed
  9. Daar S, Al Zadjali S, Alkindi S, Wali Y, Al-Rawas A, Al-Haddabi H, Al-Riyami AZ, Haemoglobin Fontainebleau (HBA2: c. 64G>C) in Oman: molecular and haematological characteristics and interaction with various haemoglobinopathies., J. Clin. Pathol. , 2017 PubMed
  10. Sidhwa K, Daruwalla MR, Pawar R, Nadkarni A, Hariharan P, Mehta P, Gupta AD, Diagnostic challenges posed by a rare alpha globin chain variant Hb Fontainebleau in a pregnant female and its potential effects in her children in view of multiple globin gene defects in her husband., Indian J Pathol Microbiol, 62(2), 323-325, 2019 PubMed
  11. Ghadami Elham,Tamaddoni Ahmad,Sedaghat Sadegh,Tabaripour Reza,Pourreza Baboli Hadis,Akhavan-Niaki Haleh, First Report of Association Between Rare α-Thalassemia Mutation (HBA1: c.298A>T) and Hb Fontainebleau (HBA2: c.64G>C)., Indian J Clin Biochem, 1(1), 115-117, 2020 PubMed
Created on 2010-06-16 16:13:15, Last reviewed on 2021-04-05 16:45:29 (Show full history)

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