IthaID: 481
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Benign / Likely Benign |
|---|---|---|---|
| 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.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
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 |
In silico pathogenicity prediction
Publications / Origin
- 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
- 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
- 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
- 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
- Turner A, Sasse J, Varadi A, Hb Fontainebleau (HBA2: c.64G > C) in the United Arab Emirates., Hemoglobin, 38(3), 216-20, 2014
- 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
- 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
- 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
- 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
- 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
- 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