title: Rapid molecular prenatal diagnosis of ataxia-telangiectasia by direct mutational analysis.
abstract: Mutations of the ataxia-telangiectasia-mutated (ATM) gene are responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T). This study reports the first A-T prenatal diagnosis performed in Spain by direct molecular analysis. The pregnant woman had a previous child suffering from A-T due to a deletion in the ATM gene. The ATM coding region was sequenced in the A-T patient and her parents. Then, a specific polymerase chain reaction (PCR) to detect the deletion was performed for prenatal diagnosis. Additionally, polymorphic HLA loci were examined in order to exclude the possible contamination by maternal DNA. In this family of Gypsy origin, we carried out a rapid molecular diagnosis of A-T. Then, a prenatal diagnosis was carried out, identifying the deletion in the fetal DNA. Additionally, we performed a population study in unrelated Spanish Gypsies and in unrelated controls, showing that the deletion described could be a hotspot in the Spanish Gypsy population. The size of the coding region and the genomic structure, together with the absence of hotspots, make the mutation screening of the ATM gene difficult. The ability to identify ATM mutations provides a tool that can be applied in confirmatory diagnosis, genetic counselling, carrier prediction and prenatal diagnosis.
authors.forename: Esther
authors.initials: E
authors.lastname: Mancebo
authors.forename: Iván
authors.initials: I
authors.lastname: Bernardo
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Castro
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Fernández-Martinez
authors.forename: Emilia
authors.initials: E
authors.lastname: Barreiro
authors.forename: Paloma
authors.initials: P
authors.lastname: De-Pablos
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Marin
authors.forename: Silvia
authors.initials: S
authors.lastname: Cortezon
authors.forename: Estela
authors.initials: E
authors.lastname: Paz-Artal
authors.forename: Luis M
authors.initials: LM
authors.lastname: Allende
mesh_terms: D001260:Ataxia Telangiectasia / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D025202:Molecular Diagnostic Techniques; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*