title: 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 beta-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 alpha-thalassemia defects were characterized.
authors.affiliation: MGC Department of Human Genetics, Leiden University, Leiden, The Netherlands. piero@ruly46.medfac.leidenuniv.nl
authors.forename: P C
authors.initials: PC
authors.lastname: Giordano
authors.forename: C L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: A J
authors.initials: AJ
authors.lastname: Heister
authors.forename: D
authors.initials: D
authors.lastname: Batelaan
authors.forename: P
authors.initials: P
authors.lastname: van Delft
authors.forename: R
authors.initials: R
authors.lastname: Plug
authors.forename: M
authors.initials: M
authors.lastname: Losekoot
authors.forename: L F
authors.initials: LF
authors.lastname: Bernini