Skip to main content
  • Correspondence
  • Open access
  • Published:

Further observation of Hemoglobin Fontainebleau (a21(B2) Ala-Pro) in a Turkish family

To the Editor,

Several hemoglobin (Hb) variants have been reported in Turkish population [1,2,3]. Herein, we represent a nucleotide alteration of the alpha-2 chain variant, Hemoglobin Fontainebleau (a21(B2) Ala-Pro) in an 8-year-old male Turkish child living in Ankara, Turkey. He was admitted to the Hospital Pediatrics Department for routine check-up. His physical examination was normal, and there was no positive consanguinity between his parents. High red blood cell count and low mean corpuscular volume were detected in complete blood count (CBC) (Fig. 1a). High-performance liquid chromatography (HPLC) showed an asymmetry (shoulder formation) in the descending part of A0 and in the A2 curve. Levels of HbA, HbA2, and HbF were observed as 93.25%, 3.55%, and 1.07%, respectively (Fig. 1a). His mother and 6-year-old sister were also screened. Their HPLC chromatograms showed similar pattern (Fig. 1b, c).

Fig. 1
figure 1

CBC, HPLC chromatograms, and HBA2 gene. The figure includes the HPLC histograms and HBA2 gene sequence analysis below the complete blood count and ferritin levels of the patient (a), his mother (b), and sister (c). The asymmetry (shoulder formation) in the descending part of A0 and in the A2 curve was indicated with an arrow on the chromatogram

Sequence analysis of HBA1 and HBA2 genes were performed by using MiSeq next-generation sequencing (NGS) platform (Illumina, San Diego, CA, USA). Genomic DNA was extracted by using the QIAamp DNA Blood Midi Kit (Qiagen, Hilden, Germany). All coding regions and exon-intron boundaries of the genes were amplified using PCR primers, designed with PRIMER©-Primer Designer v.2.0 (Scientific & Educational Software programme) software. Alignment was done by using hg19 genome with MiSeq Reporter software (Illumina Inc.), and analysis was done with IGV 2.3 (Broad Institute) software. These genes were also tested for common deletions with MLPA (multiplex ligation-dependent probe amplification) method (SALSA MLPA P140 HBA probemix, MRC Holland, Amsterdam, Holland). NM_000558.5(HBA1):c.64G>C (p.Ala22Pro) was detected by sequence analysis while MLPA test was normal (Fig. 1a, b).

Written informed consent for genetic analysis was obtained both from the child’s parents and from the mother.

Hemoglobin Fontainebleau (a21(B2) Ala-Pro) is a rarely reported hemoglobin variant. It was first reported in an Italian family without DNA analysis in 1989 and later on in India, Canada, South Cyprus, United Arab Emirates, Iraq (family living in New Zealand), and Turkey. It was described as a silent mutation and was also reported in combination with heterozygote forms of sickle cell, hereditary spherocytosis, and Hb Punjab [1, 4,5,6].

It is interesting that the cases identified were on historical migration routes. Since Turkey is located at the intersection of two continents, it is not surprising that many different hemoglobin variants are observed. Further observation of Hb Fontainebleau (a21(B2) Ala-Pro) suggests that this variant is found sporadically in the Turkish population.

Availability of data and materials

The authors can confirm that all relevant data are included in the manuscript.



Complete blood count




High-performance liquid chromatography


Multiplex ligation-dependent probe amplification


Next-generation sequencing


  1. Altay C (2002) Abnormal hemoglobins in Turkey. Turk J Haematol 19:63–74

    CAS  PubMed  Google Scholar 

  2. Akar E, Akar N (2007) A review of abnormal hemoglobins in Turkey. Turk J Hematol 24:143–145

    CAS  Google Scholar 

  3. Akar N (2014) An updated review of abnormal hemoglobins in the Turkish population. Turk J Haematol 31(1):97–98

    Article  Google Scholar 

  4. Wajcman H, Blouquit Y, Gombaud-Daintonge G, Riou J, Galacteros F (1989) Hb Fontainebleau alpha 21(B2)Ala–Pro, a new silent mutant hemoglobin. Hemoglobin 13:421

    Article  CAS  Google Scholar 

  5. Upadhye DS, Jain D, Nair SB, Nadkarni AH, Ghosh K, Colah RB (2012) 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 65:654–659

    Article  CAS  Google Scholar 

  6. Rodríguez-Capote K, Estey MP, Barakauskas V, Bordeleau P, Christensen CL, Zuberbuhler P, Higgins TN (2015) A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy. Clin Biochem 48(13–14):904–907

    Article  Google Scholar 

Download references


Not applicable.


No funding was received.

Author information

Authors and Affiliations



NA contributed to the clinical diagnosis and reviewing of the manuscript. SC contributed to the sequence analysis. YAA contributed to the drafting and reviewing of the manuscript. GST contributed to the drafting of the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Yasemin Ardicoglu Akisin.

Ethics declarations

Ethics approval and consent to participate

Each author has participated sufficiently in the work to take public responsibility for the content, and also, the authors had no conflict of interest to declare in relation to this manuscript. As it was a retrospective study, ethics approval was not taken.

Consent for publication

Written informed consent for genetic analysis and publication was obtained from the patient’s family.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Akar, N., Ceylaner, S., Akisin, Y.A. et al. Further observation of Hemoglobin Fontainebleau (a21(B2) Ala-Pro) in a Turkish family. Egypt J Med Hum Genet 21, 3 (2020).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: