Cicenia Marianna, Alesi Viola, Orlando Valeria, Magliozzi Monia, Di Tommaso Silvia, Iodice Francesca G, Pompei Emanuela, Toscano Alessandra, Digilio Maria C, Drago Fabrizio, Novelli Antonio, Baban Anwar
The European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Pediatric Cardiology and Arrhythmia/Syncope Units, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Am J Med Genet A. 2022 Mar;188(3):883-895. doi: 10.1002/ajmg.a.62598. Epub 2021 Dec 13.
Deletions involving the distal portion of the short arm of chromosome 8(8p23.1) show a high phenotypic variability. Congenital heart diseases (CHD) are often described. GATA4 when mutated or deleted is reported to be involved in cardiac morphogenesis. Only twice, left ventricular non compaction (LVNC) was reported in literature in association with 8p23.1 deletion. The present cohort includes five new patients with 8p23.1 deletions including GATA4. The spectrum of CHD is variable. Moreover, in four patients, LV hypertrabeculation was detected and in the fifth LVNC was recognized. Literature revision identified 45 patients with 8p23.1 deletions (encompassing GATA4) and heart involvement. It included wide spectrum of CHD including: heterotaxy spectrum 7/45 (15, 6%), atrioventricular canal 14/45 (balanced 3/45 including two of them with hypoplastic aortic arch; unbalanced 4/45, Fallot-AVC 1/45, partial AVC 3/45, unspecified 3/45), predominant major left heart lesions included 2/45 (4, 4%): interrupted aortic arch and hypoplastic left heart syndrome. Left ventricular hypertrabeculation might be potentially underestimated in patients with 8p23.1 deletion. These might suggest the importance of including microarray analysis in this group of patients. Moreover, 8p23.1 microdeletion or GATA4 variants can be considered in heterotaxy genetic panels.
涉及8号染色体短臂远端部分（8p23.1）的缺失表现出高度的表型变异性。先天性心脏病（CHD）经常被描述。据报道，GATA4发生突变或缺失时参与心脏形态发生。文献中仅两次报道左心室心肌致密化不全（LVNC）与8p23.1缺失相关。本队列包括五名新的8p23.1缺失患者，其中包括GATA4。CHD的谱系是可变的。此外，在四名患者中检测到左心室小梁增多，在第五名患者中识别出LVNC。文献复习确定了45名8p23.1缺失（包括GATA4）且有心脏受累的患者。其中包括广泛的CHD谱系，包括：内脏反位谱系7/45（15.6%）、房室管畸形14/45（平衡型3/45，其中两人合并主动脉弓发育不全；不平衡型4/45，法洛四联症-房室管畸形1/45，部分房室管畸形3/45，未明确类型3/45）、主要的左心病变占2/45（4.4%）：主动脉弓中断和左心发育不全综合征。8p23.1缺失患者的左心室小梁增多可能存在潜在低估。这可能提示在这组患者中进行微阵列分析的重要性。此外，8p23.1微缺失或GATA4变异可在异态性遗传检测板中考虑。
