title: SNP array and phenotype correlation shows that FLI1 deletion per se is not responsible for thrombocytopenia development in Jacobsen syndrome.
abstract: Jacobsen syndrome (JBS) is a rare chromosomal disorder caused by terminal deletion of the long arm of chromosome 11. We report on four prenatally diagnosed patients with JBS with variable prenatal and postnatal phenotypes and 11q deletions of varying sizes. Precise characterization of the deleted region in three patients was performed by SNP arrays. The severity of both the prenatal and postnatal phenotypes did not correlate with the size of the haploinsufficient region. Despite the large difference in the deletion size (nearly 6 Mb), both of the live-born patients had similar phenotypes corresponding to JBS. However, one of the most prominent features of JBS, thrombocytopenia, was only present in the live-born boy. The girl, who had a significantly longer deletion spanning all four genes suspected of being causative of JBS-related thrombocytopenia (FLI1, ETS1, NFRKB, and JAM3), did not manifest a platelet phenotype. Therefore, our findings do not support the traditional view of deletion size correlation in JBS or the causative role of FLI1, ETS1, NFRKB, and JAM3 deletion per se for the development of disease-related thrombocytopenia.
authors.affiliation: Gennet, Centre for Fetal Medicine, Praha, Czech Republic. marie.trkova@gennet.cz
authors.forename: Marie
authors.initials: M
authors.lastname: Trkova
authors.forename: Vera
authors.initials: V
authors.lastname: Becvarova
authors.forename: Martin
authors.initials: M
authors.lastname: Hynek
authors.forename: Lenka
authors.initials: L
authors.lastname: Hnykova
authors.forename: Eva
authors.initials: E
authors.lastname: Hlavova
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kreckova
authors.forename: Eduard
authors.initials: E
authors.lastname: Kulovany
authors.forename: David
authors.initials: D
authors.lastname: Cutka
authors.forename: Jitka
authors.initials: J
authors.lastname: Zatloukalova
authors.forename: Kristyna
authors.initials: K
authors.lastname: Markova
authors.forename: Martina
authors.initials: M
authors.lastname: Sukova
authors.forename: Jiri
authors.initials: J
authors.lastname: Horacek
authors.forename: David
authors.initials: D
authors.lastname: Stejskal
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D054868:Jacobsen Distal 11q Deletion Syndrome / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics*; D013921:Thrombocytopenia / Q000235:genetics*; D055815:Young Adult
chemical_list: C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1