Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children’s Hospital, Houston, TX, USA
Laurie Robak
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children’s Hospital, Houston, TX, USA
David Chitayat
The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for SickKids, University of Toronto, Toronto, ON, Canada
Claire Botsford
The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
Sarah Jurgensmeyer
Division of Genetics, Genomics, and Metabolism, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Peter Leahy
Division of Genetics, Genomics, and Metabolism, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Summary: 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.
