McGivern Bobbi, Morrow Michelle M, Torti Erin, McWalter Kirsty, Wentzensen Ingrid M, Monaghan Kristin G, Gerard Amanda, Robak Laurie, Chitayat David, Botsford Claire, Jurgensmeyer Sarah, Leahy Peter, Kruszka Paul
GeneDx, LLC, Gaithersburg, MD, USA.
GeneDx, LLC, Gaithersburg, MD, USA.
HGG Adv. 2025 Jan 9;6(1):100387. doi: 10.1016/j.xhgg.2024.100387. Epub 2024 Nov 26.
MGA (OMIM: 616061) encodes a dual-specificity transcription factor that regulates the expression of Max-network and T-box family target genes, important in embryogenesis. Previous studies have linked MGA to various phenotypes, including neurodevelopmental disorders, congenital heart disease, and early-onset Parkinson's disease. Here, we describe the clinical phenotype of individuals with de novo, heterozygous predicted loss-of-function variants in MGA, suggesting a unique disorder involving both neurodevelopmental and congenital anomalies. In addition to developmental delays, certain congenital anomalies were present in all individuals in this cohort including cardiac anomalies, male genital malformations, and craniofacial dysmorphisms. Additional findings seen in multiple individuals in this cohort include hypotonia, abnormal brain imaging, hearing loss, sleep dysfunction, urinary issues, skeletal abnormalities, and feeding difficulties. These findings provide support for MGA as a gene intolerant to protein truncation with a broad phenotypic spectrum.
MGA（在线人类孟德尔遗传数据库编号：616061）编码一种双特异性转录因子，该因子调节Max网络和T盒家族靶基因的表达，这些基因在胚胎发育过程中起着重要作用。先前的研究已将MGA与多种表型联系起来，包括神经发育障碍、先天性心脏病和早发性帕金森病。在此，我们描述了携带MGA基因新生杂合预测功能丧失变异个体的临床表型，提示这是一种涉及神经发育和先天性异常的独特疾病。除发育迟缓外，该队列中的所有个体均存在某些先天性异常，包括心脏异常、男性生殖器畸形和颅面畸形。该队列中多个个体出现的其他发现包括肌张力减退、脑部影像学异常、听力丧失、睡眠功能障碍、泌尿问题、骨骼异常和喂养困难。这些发现支持了MGA作为一个对蛋白质截短不耐受且具有广泛表型谱的基因。
