SNP array and phenotype correlation shows that FLI1 deletion per se is not responsible for thrombocytopenia development in Jacobsen syndrome

Trková, Marie; Bečvářová, Věra; Hynek, M.; Hnykova, Lenka; Hlavova, E.; Kreckova, Gabriela; Kulovaný, E; Čutka, David; Zatloukalova, Jitka; Markova, Kristyna; Suková, Martina; Horáček, J; Stejskal, D.

doi:10.1002/ajmg.a.35537

Cited by 7 publications

(11 citation statements)

References 26 publications

(32 reference statements)

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“…Ocular, hearing, hormonal and immunological problems such as late-onset combined immunodeficiency associated with hypogammaglobulinemia, pancytopenia, and low Thelper cell counts may also be present [Trkova et al, 2012]. Nearly all described JBS patients are born with Paris-Trousseau syndrome, a transient neonatal thrombocytopenia associated with hemizygosity of chromosome 11q which usually includes the FLI1 gene [Hart et al, 2000].…”

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confidence: 99%

Complex Mosaic Ring Chromosome 11 Associated with Hemizygous Loss of 8.6 Mb of 11q24.2qter in Atypical Jacobsen Syndrome

et al. 2016

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Jacobsen syndrome (JBS) is a contiguous gene deletion syndrome involving terminal chromosome 11q. The haploinsufficiency of multiple genes contributes to the overall clinical phenotype, which can include the variant Paris-Trousseau syndrome, a transient thrombocytopenia related to FLI1 hemizygous deletion. We investigated a boy with features of JBS using classic cytogenetic methods, FISH and high-resolution array CGH. The proband was found to have a mosaic ring chromosome 11 resulting in a hemizygous 11q terminal deletion of 8.6 Mb, leading to a copy number loss of 52 genes. The patient had a hemizygous deletion in the FLI1 gene region without apparent thrombocytopenia, and he developed diabetes mellitus type I, which has not previously been described in the spectrum of disorders associated with JBS. The relationship of some of the genes within the context of the phenotype caused by a partial deletion of 11q has provided insights concerning the developmental anomalies presented in this patient with atypical features of JBS.

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confidence: 99%

Complex Mosaic Ring Chromosome 11 Associated with Hemizygous Loss of 8.6 Mb of 11q24.2qter in Atypical Jacobsen Syndrome

et al. 2016

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“…Apparently, the platelet defect detected at 15 months, motor delay and mild tricuspid regurgitation could have a relationship with the ST3GAL4 , KIRREL3 and ETS1 genes, respectively, although these findings are not always present in JBS with happloinsuficiency of these genes [Grewal et al, 2008;Ji et al, 2010;Bae et al, 2011;Luukkonen et al, 2012;Trkova et al, 2012;Sheth et al, 2014;So et al, 2014].…”

Section: Discussionmentioning

confidence: 65%

“…It is noteworthy that the ST3GAL4 gene associated with thrombocytopenia has not been mentioned in any previous study; we consider that thrombocytopenia could be related to this gene defect in JBS [Grossfeld et al, 2004]. However, not all cases with a deletion in the ST3GAL4 gene are diagnosed with thrombocytopenia Trkova et al, 2012, Sheth et al, 2014So et al, 2014]. This denotes that there is no genotype-phenotype correlation in JBS ( table 1 ).…”

Section: Discussionmentioning

confidence: 67%

“…The FLI1 gene, involved in the vascular and megakaryocyte differentiation, has been related to thrombocytopenia, although it has a recessive pattern [Spyropoulos et al, 2000;Trkova et al, 2012]. It is important to mention that the FLI1 gene defect is the major cause of Paris-Trousseau syndrome (PTS); in vitro studies demonstrate that overexpression of FLI1 in CD34(+) cells from PTS patients restores the megakaryopoiesis, indicating that FLI1 hemizygous deletion contributes to the PTS hematopoietic defects [Raslova et al, 2004;Favier et al, 2015].…”

Section: Discussionmentioning

confidence: 99%

“…Behavioral and psychiatric disorders, hearing, immunological and hormonal problems have also been observed [Grossfeld et al, 2004;Manolakos et al, 2009;Mattina et al, 2009;Seppänen et al, 2014;Akshoomoff et al, 2015;Favier et al, 2015]. Several patients with 11q23.3q25 deletions ranging in size from 2.8 to 14 Mb revealed by molecular karyotyping have been reported, but only 17 patients have complete clinical data [Wenger et al, 2006;Bernaciak et al, 2008;Tyson et al, 2008;Manolakos et al, 2009;Ji et al, 2010;Wu et al, 2010;Ye et al, 2010;Guerin et al, 2012, Trkova et al, 2012Sheth et al, 2014;So et al, 2014;Xu et al, 2014;Malia et al, 2015;Maruani et al, 2015;Yamamoto et al, 2015]. The purpose of this study is to report the SNP microarraybased molecular characterization of a patient with a mild phenotype of JBS and a 11q23.3q25 deletion.…”

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confidence: 99%

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Jacobsen Syndrome: Surgical Complications due to Unsuspected Diagnosis, the Importance of Molecular Studies in Patients with Craniosynostosis

Chávez

López²,

Miranda

et al. 2015

Mol Syndromol

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Jacobsen syndrome (JBS) is an uncommon contiguous gene syndrome. About 85-92% of cases have a de novo origin. Clinical variability and severity probably depend on the size of the affected region. The typical clinical features in JBS include intellectual disability, growth retardation, craniofacial dysmorphism as well as craniosynostosis, congenital heart disease, and platelet abnormalities. The proband was a 1 year/3-month-old Mexican male. Oligonucleotide-SNP array analysis using the GeneChip Human Cytoscan HD was carried out for the patient from genomic DNA. The SNP array showed a 14.2-Mb deletion in chromosome 11q23.3q25 (120,706-134,938 Mb), which involved 163 RefSeq genes in the database of genomic variation. We report a novel deletion in JBS that increases the knowledge of the variability in the mutation sites in this region and expands the spectrum of molecular and clinical defects in this syndrome.

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Periventricular nodular heterotopia and transverse limb reduction defect in a woman with interstitial 11q24 deletion in the Jacobsen syndrome region

Stockley

Stavropoulos

2013

American J of Med Genetics Pt A

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Jacobsen syndrome (JS) is a disorder of developmental delay, growth retardation, thrombocytopenia, dysmorphic features, and cardiac abnormalities, among other congenital anomalies. JS is caused by contiguous gene deletion in distal chromosome 11q, generally varying in size from 7 to 20 Mb. Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder in which neurons are abnormally located in nodules along the edges of the lateral ventricles. PVNH can also be seen with other congenital anomalies, including a recurrent association with distal limb defects. Transverse limb defects have previously been reported in two patients with JS. We report on a patient with a 3.162 Mb interstitial deletion at chromosome region 11q24 overlapping the region commonly affected in JS. The patient had PVNH and a transverse limb reduction defect, with minimal typical findings of JS. This is the first report of PVNH associated with a microdeletion at chromosome 11q and may represent an expansion of the phenotypic spectrum associated with JS. This is the third report of transverse limb reduction defects in association with JS, supporting a widening of the skeletal phenotypic spectrum in JS to include more severe limb anomalies. ETS1 is proposed as a candidate gene for involvement in limb anomalies in JS.

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SNP array and phenotype correlation shows that FLI1 deletion per se is not responsible for thrombocytopenia development in Jacobsen syndrome

Cited by 7 publications

References 26 publications

Complex Mosaic Ring Chromosome 11 Associated with Hemizygous Loss of 8.6 Mb of 11q24.2qter in Atypical Jacobsen Syndrome

Complex Mosaic Ring Chromosome 11 Associated with Hemizygous Loss of 8.6 Mb of 11q24.2qter in Atypical Jacobsen Syndrome

Jacobsen Syndrome: Surgical Complications due to Unsuspected Diagnosis, the Importance of Molecular Studies in Patients with Craniosynostosis

Periventricular nodular heterotopia and transverse limb reduction defect in a woman with interstitial 11q24 deletion in the Jacobsen syndrome region

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