MGA-Related Syndrome: A Proposed Novel Disorder

Authors

Bobbi McGivern
Michelle M Morrow
Erin Torti
Kirsty McWalter
Ingrid M Wentzensen
Kristin G Monaghan
Amanda Gerard
Laurie Robak
David Chitayat
Claire Botsford
Sarah Jurgensmeyer
Peter Leahy
Paul Kruszka

Publication Date

1-9-2025

Journal

Human Genetics and Genomics Advances

DOI

10.1016/j.xhgg.2024.100387

PMID

39600096

PMCID

PMC11699453

PubMedCentral® Posted Date

11-26-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Male, Female, Phenotype, Child, Preschool, Child, Syndrome, Infant, Adolescent, Transcription Factors, MGA, clinical exome sequencing, candidate gene, gene discovery, congenital anomalies, neurodevelopmental disorder, craniofacial dysmorphism, congenital heart defect, hearing loss, genetic testing

Abstract

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.

Comments

Associated Data