11q24.2q24.3 microdeletion in two families presenting features of Jacobsen syndrome, without intellectual disability Role of FLI1, ETS1, and SENCR long noncoding RNA

Solène Conrad (1) , Florence Demurger (2) , Kamran Moradkhani (1) , Olivier Pichon (1) , Cédric Le Caignec (1) , Cécile Pascal (3) , Caroline Thomas (1) , Sophie Bayart (4) , Antoinette Perlat (4) , Christèle Dubourg (5, 4) , Sylvie Jaillard (4, 6) , Mathilde Nizon (7, 8)

1 CHU Nantes - Centre Hospitalier Universitaire de Nantes
2 Génétique médicale [Centre Hospitalier de Vannes]
3 Hôpital privé du Confluent [Nantes]
4 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
5 IGDR - Institut de Génétique et Développement de Rennes
6 Irset - Institut de recherche en santé, environnement et travail
7 Service de génétique médicale [CHU Nantes]
8 ITX - ITX - unité de recherche de l'institut du thorax

This report presents two families with interstitial 11q24.2q24.3 deletion, associated with malformations, hematologic features, and typical facial dysmorphism, observed in Jacobsen syndrome (JS), except for intellectual disability (ID). The smallest 700 Kb deletion contains only two genes FLI1 and ETS1, and a long noncoding RNA, SENCR, narrowing the minimal critical region for some features of JS. Consistent with recent literature, it adds supplemental data to confirm the crucial role of FLI1 and ETS1 in JS, namely FLI1 in thrombocytopenia and ETS1 in cardiopathy and immune deficiency. It also supports that combined ETS1 and FLI1 haploinsufficiency explains dysmorphic features, notably ears, and nose anomalies. Moreover, it raises the possibility that SENCR, a long noncoding RNA, could be responsible for limb defects, because of its early role in endothelial cell commitment and function. Considering ID and autism spectrum disorder, which are some of the main features of JS, a participation of ETS1, FLI1, or SENCR cannot be excluded. But, considering the normal neurodevelopment of our patients, their role would be either minor or with an important variability in penetrance. Furthermore, according to literature, ARHGAP32 and KIRREL3 seem to be the strongest candidate genes in the 11q24 region for other Jacobsen patients.

Mots clés: Jacobsen syndrome; SENCR; 11q24 deletion; ARHGAP32; ETS1; FLI1

Domaines: Sciences du Vivant [q-bio]; Génétique

Solène Conrad, Florence Demurger, Kamran Moradkhani, Olivier Pichon, Cédric Le Caignec, et al.. 11q24.2q24.3 microdeletion in two families presenting features of Jacobsen syndrome, without intellectual disability Role of FLI1, ETS1, and SENCR long noncoding RNA. American Journal of Medical Genetics Part A, 2019, 179 (6), pp.993-1000. ⟨10.1002/ajmg.a.61113⟩. ⟨hal-02091219⟩