Indian Journal of Human Genetics
Home Current Issue Archives Guidelines Subscriptions e-Alerts Login 
Users online: 18
Print this page  Email this page Small font sizeDefault font sizeIncrease font size


 
            Table of Contents  
CASE REPORT
Year : 2013  |  Volume : 19  |  Issue : 3  |  Page : 352-354
 

Hemoglobin Fontainebleau [a21(B2)Ala>Pro]: The second report from India


1 Department of Hematopathology, Christian Medical College, Ludhiana, Punjab, India
2 National Institute of Immunohaematology, Mumbai, Maharashtra, India
3 Department of Pathology, Christian Medical College, Ludhiana, Punjab, India

Date of Web Publication30-Oct-2013

Correspondence Address:
Sheila Das
Department of Pathology, Christian Medical College, Ludhiana, Punjab - 141 008
India
Login to access the Email id

Source of Support: Financial support from Indian Council of Medical Research for conducting this study, Conflict of Interest: None


DOI: 10.4103/0971-6866.120822

Get Permissions

 

   Abstract 

Structural hemoglobin (Hb) variants are mainly due to point mutations in the globin genes resulting in single amino acid substitutions. Until date, about 200 alpha chain variants have been identified and they are usually detected during the hemoglobinopathy screening programs. Under a community control program for hemoglobinopathies, which involved screening of antenatal cases followed by prenatal diagnosis if indicated. Here, we report a rare alpha globin gene variant Hb Fontainebleau [a21(B2)Ala>Pro] detected in the heterozygous condition in a 35-year-old pregnant lady screened during this program. This is the second report of this alpha globin variant from India. Unlike the earlier case from India where Hb Fontainebleau was reported in a neonate who was also a carrier of Hb Sickle and had no clinical problems, this case presented with a bad obstetric history associated with the secondary infertility. However, the presence of the variant and the obstetric complications may be unrelated.


Keywords: Alpha globin gene variant, hemoglobin Fontainebleau, infertility


How to cite this article:
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 2013;19:352-4

How to cite this URL:
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 [serial online] 2013 [cited 2016 May 24];19:352-4. Available from: http://www.ijhg.com/text.asp?2013/19/3/352/120822



   Introduction Top


Structural hemoglobin (Hb) variants are mainly due to point mutations in α or β globin genes resulting in single amino acid substitutions. Until date, around 1000 Hb variants have been identified out of which at least 200 are alpha chain variants. [1] Many of these variants do not cause any problems and therefore remain undetected in the population. They are often picked up only when a large screening program on hemoglobinopathies is undertaken in the general population. Few alpha chain variants like Hb Sallanches, though asymptomatic in the heterozygous condition cause severe Hb H disease in the homozygous condition. [2] Until date, four cases of Hb Fontainebleau have been reported, including one case from India. [3],[4],[5],[6] These have all been present in combination with Hb S or a co-existing membrane defect. We report the first report of Hb Fontainebleau from India without any other co-existing hematological defect.

Christian Medical College and Hospital, Ludhiana is a tertiary care center. During the Jai Vigyan Mission Project on screening and community control of thalassemia and sickle cell disease by Indian Council of Medical Research (ICMR) from 2001 to 2004, 5000 antenatal cases (ANC) were screened, of which 4.2% were detected to have heterozygous state for beta thalassemia and 1.8% consistent with Hb D-Punjab, Hb D-Iran, Hb Q-India, Hb E and Hb S trait. Subsequently, antenatal screening continued in our institute as Phase II of the above project. An ICMR sponsored center for molecular characterization of hemoglobinopathies and prenatal diagnosis of thalassemias and sickle cell disease was established in our institute.


   Case Report Top


Recently, a 35-year-old ANC born of a non-consanguineous marriage to a Jat Sikh family from Punjab was presented for routine thalassemia screening under the antenatal screening program for thalassemia. She had no previous history of anemia or blood transfusions. She had no clinical complications other than a bad obstetric history. She had delivered a healthy baby boy at 26 years of age by a cesarean section with a low birth weight of 1.7 kg. This pregnancy was associated with pregnancy induced hypertension, oligohydramnios and intrauterine growth retardation. She had secondary infertility and later conceived on two occasions at the age of 33 and 34 years. These were high risk pregnancies associated with hypothyroidism and ended in a missed abortion at 9 weeks gestation and medical termination of pregnancy at 20 weeks gestation, respectively. No definitive cause of infertility could be ascertained.

Her Hb level was 11.9 g/dl with red blood cells (RBCs) count of 4.37 million/μl, mean cell Hb of 27.2 pg, mean cell volume of 81.9 fl and red cell distribution width 16.0%. RBCs were normocytic normochromic. High-performance liquid chromatography (HPLC) variant study showed an unknown peak of 14.9% (retention time 2.89 min), which appeared as a hump in the peak adjoining Hb A [Figure 1]. Cellulose acetate electrophoresis (pH 8.9) did not show the presence of any abnormal band. The common alpha globin gene deletions were found to be absent. Direct deoxyribonucleic acid (DNA) sequencing of the alpha globin gene showed the presence of a heterozygous G→C substitution at codon 21 leading to the substitution of alanine to proline corresponding to Hb Fontainebleau [Figure 2]. The detailed hematological and molecular findings are shown in [Table 1]. Her husband was also screened for hemoglobinopathies and showed normal red cell indices and a normal Hb chromatogram on HPLC. Other family members were not available for screening. The couple was suitably counseled.
Table 1: Hematological and molecular investigations in the case heterozygote for Hb Fontainebleau

Click here to view
Figure 1: High-performance liquid chromatography chromatogram showing the unknown peak at retention time .89 min

Click here to view
Figure 2: Electropherogram of the alpha gene showing hemoglobin Fontainebleau [a21(B2)Ala>Pro]

Click here to view



   Discussion Top


The spectrum and frequency of α globin chain variants in India remains unknown though few cases have been reported. [7] Non-deletional mutations, in general, affect the fundamental processes of globin gene expression. Hb Fontainebleau [a21(B2)Ala>Pro], is an alpha chain variant characterized by an alanine→proline substitution at codon 21 with a GCT→CCT change at the DNA level, this proline residue is located at the beginning of the alpha helix. [3] This variant has so far been identified in only four unrelated families globally. It was first reported in a 15-year-old girl of Italian origin living in France. In this case, the co-existing membrane defect, spherocytosis with Hb Fontainebleau explained the hematological abnormalities and the severe phenotype. [3] Another female individual in the same family with Hb Fontainebleau alone was clinically and hematologically normal. The second case was an adult male subject in an Iraqi family living in New Zealand. This individual had microcytosis, but this was not associated to the presence of Hb Fontainebleau. [4] The third case was identified in Cyprus while screening for thalassemia in the Greek Cypriot population. [5] The fourth family was from Madhya Pradesh, India in a newborn baby and her mother. In both these cases, this mutation was present along with a beta globin gene defect Haemoglobin Sickle Hb S. [6]

This is the second report of this Hb variant from India. Unlike the earlier case, this case had normal hematological indices, but presented with a bad obstetric history, which may just be a chance association.


   Acknowledgment Top


We thank the ICMR for financial support for conducting this study.

 
   References Top

1.Hardison RC, Chui DH, Giardine B, Riemer C, Patrinos GP, Anagnou N, et al. HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Hum Mutat 2002;19:225-33.  Back to cited text no. 1
    
2.Warang P, Nair S, Nadkarni A, Ghosh K, Colah RB. Hb H disease due to homozygosity for a rare alpha2-globin variant, Hb Sallanches. Hemoglobin 2010;34:45-8.  Back to cited text no. 2
    
3.Wajcman H, Blouquit Y, Gombaud-Saintonge G, Riou J, Galacteros F. Hb Fontainebleau alpha 21(B2) Ala - Pro, a new silent mutant hemoglobin. Hemoglobin 1989;13:421-8.  Back to cited text no. 3
    
4.Brennan SO, Chan T, Ryken S, Ruskova A. A second case of Hb Fontainebleau alpha21(B2) Ala - >Pro in an individual with microcytosis. Hemoglobin 2009;33:258-61.  Back to cited text no. 4
    
5.Kyrri AR, Felekis X, Kalogerou E, Wild BJ, Kythreotis L, Phylactides M, et al. Hemoglobin variants in Cyprus. Hemoglobin 2009;33:81-94.  Back to cited text no. 5
    
6.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 2012;65:654-9.  Back to cited text no. 6
    
7.Nair S, Nadkarni A, Warang P, Bhave A, Ghosh K, Colah R. Five alpha globin chain variants identified during screening for haemoglobinopathies. Eur J Clin Invest 2010;40:226-32.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]



 

Top
Print this article  Email this article
           

    

 
   Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (515 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
   Case Report
   Discussion
   Acknowledgment
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed730    
    Printed27    
    Emailed2    
    PDF Downloaded18    
    Comments [Add]    

Recommend this journal