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Hb Crete in a Turkish Family with Crete Island origin

Duran Canatan

Antalya Genetic Diagnostic Center – Antalya, Turkey

Hemoglobinopathy Diagnostic Center of Mediterranean Blood Diseases Foundation- Antalya, Turkey

E-mail : durancanatan@gmail.com

İbrahim Keser

Akdeniz University Medical Faculty, Department of Biology and Genetics – Antalya, Turkey

Türker Bilgen

Research and Application Centre for Scientific and Technological Investigations (NABILTEM) of Namik Kemal University- Tekirdağ, Turkey

Serpil Delibaş

Hemoglobinopathy Diagnostic Center of Mediterranean Blood Diseases Foundation- Antalya, Turkey

DOI: 10.15761/IMM.1000243

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Abstract

Hemoglobin Crete is an abnormal hemoglobin of beta chain with high oxygen affinity and neutral and unstable as electrophoretic. It is characterized by erytrocytosis and microcytosis as clinically and [beta129(H7)Ala>Pro] as molecularly. First time, it was reported a combination of beta and delta-beta mutations and also in a homozygous state in a Greek family emigrated to the United States from the island of Crete. Here in first time, we report a Turkish family with Hb Crete and thalassemic mutation IVS1.110 (G> A).

Key words

Hb Crete, turkish family, crete island

Introduction

Hemoglobin Crete is an abnormal hemoglobin of beta chain with high oxygen affinity and neutral as electrophoretic. The erytrocytosis and microcytosis is remarkable as clinically. It is characterized by Ala> Pro in beta chain [beta129 (H7) Ala>Pro] [1].  First time, it was reported a combination of beta and delta-beta mutations and also in a homozygous state in a Greek family emigrated to the United States from the island of Crete [2,3]. In our country, first case who emigrated from the island of Crete to Turkey was reported by Arslan et al. [4]. We report  a family with Hb Crete and thalassemic mutation IVS1.110 (G> A) in our country.

Case

A seventeen-year-old female patient was admitted to our center with complaints with paleness and weakness. We learned that the origin of the family emigrated to Antalya from the Crete island five generations ago. In the physical examination, she had pallor, the scar of cholecystectomy and splenomegaly. Her complete blood count (CBC) was microcytosis, hypochromia, erythrocytosis, and anizositosis in Table 1. The result of High Performance Liquid Chromatography (HPLC) showed 90% HbA1, 5.7%, HbA 2 and 4.2% HbF. Mother and father was examined , her mother had also microcytosis and erythrocytosis 96%HbA1 3.4% HbA2 and 1% HbF in HPLC, while the father had mild anemia and microcytosis besides of 93% HbA1 and 6.4% HbA2 was found in HPLC (Table 1 and 2) . We have informed constent for analysis DNA sequencing analysis. Following DNA extraction by a commercial kit (Roche, Mannheim, Germany) and amplification of the whole beta globin gene by standard protocols of PCR and DNA sequencing (Applied Biosystems, USA). We found compound heterozygous for Hb Crete (HBB:c.388 G>C) and IVS.1.110 (G>A) in case. (Figure 1) Her mother was the trait of Hb Crete (HBB:c.388 G>C) and her father was the trait of IVS1.110 (G>A) (Table2)

Table 1. The results of complete blood count in a turkish family

 

Hb (g/dl)

Hct

(%)

RBC

(1012/l)

MCV

(fl)

MCH

(p/g)

MCHC

(g/dl

RDW

(%)

Rtc

(%)

WBC

(109/l)

 

PLT

(109/l)

Case

 

12.2

39.8

7.12

53

16.1

31.0

17.7

1.2

8.2

207

Mother

14.0

 

43.5

6.57

66

21.2

32.1

18.9

1.1

7.98

269

Father

12.7

 

41

6.73

61

18.8

30.9

17.9

1.2

9.90

298

Figure 1. Hb Crete (HBB:c.388 G>C) in Beta sequence analysis

Table 2. The results of HPLC and DNA sequence analysis of beta gene in a turkish family

 

HbA (%)

HbA2

(%)

Hb F

(%)

Anormal Hb

(%)

DNA  sequence analysis of beta gene

Case

90.1

5.7

4.2

0

Hb Crete / IVS1.110

Mother

96.5

3.4

1.0

0

Hb Crete / Normal

Father

92.8

6.4

0.8

0

IVS1.110 / Normal

Discussion

Although hematological and HPLC results are normal level in Hb Crete carriers , a definitive diagnosis is established by DNA analysis, but sometimes clinically may be change in association with severe beta-thalassemia mutations. First identified case had hemolysis, erythrocytosis, abnormal red cell morphology, splenomegaly and marked erythroid hyperplasia symptoms was diagnosed Hb Crete/delta beta0 thalassemia compound heterozygous (67% Hb Crete and 30% Hb F), his father was  Hb Crete/B0 compound heterozygous thalassemia Hb Crete (84%, 5% and Hb A2 HBF 10%), and his brother was Hb Crete trait (Hb Crete 38%, 56% Hb A). (2) Two homozygous Hb Crete cases were defined in Greece and in both cases had erythrocytosis, microcytosis and mild microcytic anemia [3]. The Turkish first case had hepatosplenomegaly, extramedullary hemaotopoesis ,erythrocytosis and microcytosis . HPLC showed abnormal band (%56.9) and Hb Crete was detected in the sequence analysis of the patient [4].

We thought that our case was not an ordinary thalassemia trait, because of she had splenomegaly and cholelithiasis,  microcytosis and erythrocytosis in peripheric blood and had 90% HbA1, 5.7% HbA 2 and 4.2% HbF in HPLC. Mother and father was examined , her mother had also microcytosis and erythrocytosis besides of 96%HbA1 3.4% HbA2 and 1% HbF in HPLC, while the father had mild anemia and microcytosis besides of 93% HbA1 and 6.4% HbA2 was found in HPLC. Complete sequence analysis of the beta globin gene of case was revealed compound heterozygous for Hb Crete/IVS1.110, her mother had Hb Crete and  her father had IVS.1.110 G>A .

It has been shown by functional studies that Hb Crete is one of the causes of secondary erythrocytosis by increased erythropoietin levels [2]. Our index case and her mother carrier for Hb crete had mild erythrocytosis. We didn’t study fonctional test.

In conclusion; sometimes Hb Crete and similar abnormal hemoglobins may not be shown by HPLC, therefore the identification of their needs with sequence analysis because it is a great importance in prenatal diagnosis, genetic counseling and clinical follow-up.

Conflict of interest statement

The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included.

References

  1. Christopoulou G, Tserga A, Patrinos GP, Papadakis MN (2004) Molecular characterization and diagnosis of Hb Crete[beta129(H7)Ala-->Pro]. Hemoglobin  28: 339-42. [Crossref]
  2. Maniatis A, Bousios T, Nagel RL, Balazs T, Ueda Y, et al. (1979) Hemoglobin Crete (beta129 ala leads to pro): a new high-affinity variant interacting with betao -and delta beta0-thalassemia. Blood  54: 54-63.
  3. Papassotiriou I, Traeger-Synodinos J, Marden MC, Kister J, Liapi D, et al. (2005) The homozygous state for Hb Crete[beta129 (H7) Ala-->Pro] is associated with a complexphenotype including erythrocytosis and functionalanemia. Blood Cells Mol Dis  34: 229-34. [Crossref]
  4. Arslan Ç, Kahraman S, Özsan H, Akar (2011) Hemoglobin crete in the Turkish population. Turk J Hematol  28: 346-7. 

Editorial Information

Editor-in-Chief

Ivan Gout
University College London

Article Type

Short Communication

Publication history

Received date: September 9, 2016
Accepted date: September 22, 2016
Published date: September 26, 2016

Copyright

© 2016 Canatan D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Canatan D, Keser I, Bilgen T, Delibaş S (2016) Hb Crete in a Turkish Family with Crete Island origin. Integr Mol Med 3: DOI: 10.15761/IMM.1000243.

Corresponding author

Prof. Dr. Duran Canatan

Antalya Genetic Diagnostic Center, Arapsuyu Mh 600 Sk 39/1 , 07070 Konyaaltı-Antalya-Turkey

E-mail : durancanatan@gmail.com

Table 1. The results of complete blood count in a turkish family

 

Hb (g/dl)

Hct

(%)

RBC

(1012/l)

MCV

(fl)

MCH

(p/g)

MCHC

(g/dl

RDW

(%)

Rtc

(%)

WBC

(109/l)

 

PLT

(109/l)

Case

 

12.2

39.8

7.12

53

16.1

31.0

17.7

1.2

8.2

207

Mother

14.0

 

43.5

6.57

66

21.2

32.1

18.9

1.1

7.98

269

Father

12.7

 

41

6.73

61

18.8

30.9

17.9

1.2

9.90

298

Figure 1. Hb Crete (HBB:c.388 G>C) in Beta sequence analysis

Table 2. The results of HPLC and DNA sequence analysis of beta gene in a turkish family

 

HbA (%)

HbA2

(%)

Hb F

(%)

Anormal Hb

(%)

DNA  sequence analysis of beta gene

Case

90.1

5.7

4.2

0

Hb Crete / IVS1.110

Mother

96.5

3.4

1.0

0

Hb Crete / Normal

Father

92.8

6.4

0.8

0

IVS1.110 / Normal