RESUMO
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.
Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Síndrome da Deleção Distal 11q de Jacobsen/diagnóstico , Síndrome da Deleção Distal 11q de Jacobsen/genética , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-fli-1/genética , RNA Longo não Codificante , Hibridização Genômica Comparativa , Fácies , Feminino , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Cariotipagem , Masculino , Linhagem , FenótipoRESUMO
We describe a 19-month-old male presenting with right stenotic megaureter, anemia and thrombocytopenia, cardiac and ophthalmologic abnormalities. Analysis with array-based comparative genomic hybridization (aCGH) revealed an interstitial deletion of about 2.4 Mb of chromosome 11q24.2q24.3. We compared the phenotype of our patient with that of recently reported patients studied by aCGH, who showed an overlapping deletion. We also analysed the gene content of the deleted region in order to investigate the possible involvement of specific genes in the clinical phenotype.