Phenotypic diversity in beta-HbE thalassemia patients

  • Pustika Amalia Wahidiyat
  • Djajadiman Gatot
  • Tenny Tjitrasari
  • Harapan Parlindungan Ringoringo
  • N S Marzuki
  • R A Taufani
  • I Setianingsih
  • A Harahap
Keywords: thalassemia, phenotype, mutation

Abstract

Background Thalassemia is a monogenic disease, yet the clini-
cal manifestations (phenotype) are variable although they have
the same genotype. The clear-cut correlation between genotype
and phenotype in β-thalassaemia/HbE patients remains unex-
plained. There are several factors that play a role in the severity of
the clinical manifestations, i.e. two alpha-gene deletion, homozy-
gote Xmn1 polymorphism +/+, -+-++, ++-++ haplotype, and hemo-
globin Constant Spring.
Objective To understand the clinical diversity of patients with HbE/
α thalassemia and to determine whether it is possible to predict
phenotypic severity from genetic factors.
Methods A descriptive study on clinical presentations and hema-
tological data of beta-HbE thalassemia patients. DNA analysis was
performed to detect β-thalassemia mutations and the ameliorating
factors (alpha-globin genes deletions and Xmn1 restriction site poly-
morphism at position –158 upstream of the G γ-globin gene) which
were already known.
Results Thirty patients with HbE/β thalassemia (4 to 29 years old)
were recruited. IVS1-nt5 (G>C) severe β + mutation was detected
in 20 patients. Eighteen of 20 patients with positive IVS1-nt5 mu-
tation group were heterozygous for Xmn1 restriction site polymor-
phism and none of the patients was co-inherited with two á-globin
gene deletion. Almost all patients (19/20) with positive IVS1-nt5
mutation group required regular transfusions, yet the mean age at
first blood transfusion was older in negative IVS1-nt5 mutation group
than that of positive IVS1-nt5 mutation group (5.7 vs 4 years). Mean
hemoglobin before initial transfusion was higher in negative IVS1-
nt5 mutation group than that of positive IVS1-nt5 mutation group
(5.88 vs 5.39 g/dl). The mean total transfusion per year was lower
in the negative IVS1-nt5 mutation group than that of positive IVS1-
nt5 mutation group (190.6 vs 215.1 ml/year).
Conclusions Beta-HbE thalassemia patients with identical beta
thalassemia mutation (IVS1-nt5) show remarkable clinical diver-
sity. Neither two alpha-gene deletion, nor the Xmn1- G γ polymor-
phism can explain the phenotypic variation. Other ameliorating
determinants or genetic modifications responsible for the variable
clinical severity remain to be explored.

Author Biographies

Pustika Amalia Wahidiyat
Haematology Division, Department of Child Health, University
of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Djajadiman Gatot
Haematology Division, Department of Child Health, University
of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Tenny Tjitrasari
Haematology Division, Department of Child Health, University
of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Harapan Parlindungan Ringoringo
Haematology Division, Department of Child Health, University
of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
N S Marzuki
Eijkman Institute for Molecular Biology, University of
Indonesia, Jakarta, Indonesia
R A Taufani
Eijkman Institute for Molecular Biology, University of
Indonesia, Jakarta, Indonesia
I Setianingsih
Eijkman Institute for Molecular Biology, University of
Indonesia, Jakarta, Indonesia
A Harahap
Eijkman Institute for Molecular Biology, University of
Indonesia, Jakarta, Indonesia

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Published
2016-10-18
How to Cite
1.
Wahidiyat P, Gatot D, Tjitrasari T, Ringoringo H, Marzuki N, Taufani R, Setianingsih I, Harahap A. Phenotypic diversity in beta-HbE thalassemia patients. PI [Internet]. 18Oct.2016 [cited 12Aug.2022];46(2):82-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/906
Section
Articles
Received 2016-10-13
Accepted 2016-10-13
Published 2016-10-18