The Molecular Spectrum of Beta-Thalassemia and Abnormal Hemoglobins in the Allochthonous and Autochthonous Dutch Population

Abstract

The prevalence at birth of hemoglobin defects in the autochthonous North-European population is low. However, the long immigration and colonial history of the Netherlands has resulted in a group of about 1–2 million ‘autochthonous‘ inhabitants, with Asian, South-European or African ancestors, in whom a moderate birth prevalence of globin gene mutations can be expected. Furthermore, at least 10% of the Dutch population consists of recent immigrants from different countries with high birth prevalence of hemoglobinopathies. Because of the endogamous partner choice, which is prevalent in this population, the risk for homozygous progeny remains elevated. At least 100,000 carriers of hemoglobinopathies of recent allochthonous origin are present in the Netherlands, and the number of homozygous children is rising. Prevention by prenatal diagnosis requires a suitable protocol and knowledge about the molecular defects present in the country. Therefore we have analyzed a large number of patients and carriers, both at the hematological and at the DNA level. Our survey revealed 47 different β-thalassemia determinants, characterized on 223 independent chromosomes from individuals of different ethnic origins. As expected, the most prevalent mutations were largely represented. The cd39 (C→T) mutation was found in 70% of the immigrants from Morocco, Sardinia and other Central-West-Mediterranean regions while the IVS-I-110 (G→A) was prevalent in the East-Mediterranean populations. The IVS-I-5 (G→C) mutation was found in 45% of the patients of Indonesian origin. We also registered 308 independent chromosomes with common structural defects (HbS, HbC, HbE, Hb Lepore, Hb Constant Spring and HbD Punjab) and 33 chromosomes with 19 different, less frequent, rare or very rare mutants. Seven structural mutants were described for the first time and published separately. Furthermore, 139 independent chromosomes with deletional and nondeletional α-thalassemia defects were characterized.

MOLECULAR SPECTRUM OF Β-Thalassemia IN THE IRANIAN PROVINCE OF HORMOZGAN

“…Nine carriers with heterozygous thalassemic phenotypes or carriers of an abnormal hemoglobin (Hb) pattern, were also included in this study. DNA was isolated from white blood cells as described previously (3). The strategy applied for the detection of point mutations consisted of screening fragments of the b-globin gene, ampli®ed by polymerase chain reaction (PCR), using the denaturing gradient gel electrophoresis (DGGE) technique, followed by con®rmation by direct sequencing of those fragments that showed an abnormal banding pattern ( Fig.…”

Implementing Neonatal Screening for Haemoglobinopathies in the Netherlands

“…2 Because carriers are protected against malaria, the disease is primarily found in countries where malaria is, or used to be, endemic. Due to human migration, the prevalence of haemoglobinopathies is now rising in other countries 3 and several prevention programmes have been organized around the world. 4 -10 Reports of low prevalence of haemoglobinopathies in the Netherlands discouraged prevention 11,12 until the contrary was proven by a series of publications, which included a study performed in 2003.…”

Paediatric allogeneic bone marrow transplantation for homozygous β-thalassaemia, the Dutch experience

“…The Hb fractions were measured either manually 17 or automatically using HPLC as previously described. 18 b/a-chain synthesis ratios were measured pre-and serially post-transplant using a rapid modified method. 19 Donor b/a-chain synthesis ratios were similarly measured pretransplant.…”