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Two new β-thalassemia deletions compromising prenatal diagnosis in an Italian and a Turkish couple seeking prevention

¹ The Reference Hemoglobinopathies Laboratory, Dept. of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
² Associazione Nazionale Microcitemie Italia (ANMI ONLUS), Centro Studi Microcitemie di Roma (CSMR), Rome, Italy
³ Laboratory of Medical Genetics, University of Athens, St. Sophia’s Children’s Hospital, Athens, Greece
⁴ Bogazici University Dept. Molecular Biology and Genetics Neurodegeneration Research Laboratory, Istanbul Turkey
⁵ Department of Biomedical Sciences and Biotechnology, University of Cagliari, Italy
⁶ Laboratory of Human Genetics and Microcitaemias, Ospedali Galliera, Genoa, Italy

Correspondence: Marion Phylipsen, The Reference Hemoglobinopathies Laboratory, Dept. of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. E-mail:m.phylipsen{at}lumc.nl

When the molecular background of couples requesting prevention is unclear, family analysis and tools to define rare mutations are essential. We report two novel deletion defects observed in an Italian and in a Turkish couple. The first proband presented with microcytic hypochromic parameters without iron deficiency, a normal HbA₂ and an elevated HbF (10.6%). His father presented with a similar phenotype and his wife was heterozygous for the common Mediterranean codon 39 (HBB:c.118C>T) mutation. Having excluded point mutations and common deletions, Multiplex Ligation-dependent Probe Amplification was performed revealing an unknown G(Aβ)⁰-thalassemia defect spanning from the A gene to downstream of the β-globin gene provisionally named Leiden 69.5 kb deletion. In the second case, the wife presented with a mild thalassemic picture, normal HbA₂, elevated HbF (18.5%) and a β/ globin chain synthesis ratio of 0.62, without iron deficiency or any known β-thalassemia defect, while the husband was a simple carrier of the common Mediterranean IVS-I-110 (HBB:c.93-21 G>A) mutation. A new large deletion involving the β-gene and part of the -gene was identified by Multiplex Ligation-dependent Probe Amplification provisionally named "Leiden 7.4 kb".

Key words: thalassemia, prevention, Multiplex Ligation-dependent Probe Amplification.