title: Two new beta-thalassemia deletions compromising prenatal diagnosis in an Italian and a Turkish couple seeking prevention.
abstract: 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 HbA(2) 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 Ggamma(Agammadeltabeta)(0)-thalassemia defect spanning from the Agamma gene to downstream of the beta-globin gene provisionally named Leiden 69.5 kb deletion. In the second case, the wife presented with a mild thalassemic picture, normal HbA(2), elevated HbF (18.5%) and a beta/alpha globin chain synthesis ratio of 0.62, without iron deficiency or any known beta-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 beta-gene and part of the delta-gene was identified by Multiplex Ligation-dependent Probe Amplification provisionally named "Leiden 7.4 kb".
authors.affiliation: The Reference Hemoglobinopathies Laboratory, Dept. of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. m.phylipsen@lumc.nl
authors.forename: Marion
authors.initials: M
authors.lastname: Phylipsen
authors.forename: Antonio
authors.initials: A
authors.lastname: Amato
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cappabianca
authors.forename: Jan
authors.initials: J
authors.lastname: Traeger-Synodinos
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kanavakis
authors.forename: Nazli
authors.initials: N
authors.lastname: Basak
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Teresa
authors.initials: T
authors.lastname: Tuveri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ivaldi
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D001483:Base Sequence / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D007558:Italy; D008297:Male; D010375:Pedigree; D017384:Sequence Deletion; D014421:Turkey; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D055544:beta-Globins