Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies

• Published in: BMC medical genomics Vol. 17; no. 1; pp. 130 - 8
• Main Authors: Tolmacheva, Ekaterina, Bolshakova, Anna S, Shubina, Jekaterina, Rogacheva, Margarita S, Ekimov, Alexey N, Podurovskaya, Julia L, Burov, Artem A, Rebrikov, Denis V, Bychenko, Vladimir G, Trofimov, Dmitry Yu, Sukhikh, Gennady T
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.05.2024; BioMed Central; BMC
• Subjects: Abnormalities, Multiple - genetics; Analysis; Atrophy; Birth defects; Brain stem; Care and treatment; Case Report; Child development; Congenital defects; Congenital diseases; Convulsions & seizures; Corpus callosum; De novo variant; Diagnosis; Epilepsy; Exome Sequencing; Expanding phenotype; Genes; Genetic aspects; Genetic disorders; Genomes; Genotype & phenotype; Hearing loss; Heart; Humans; Infant; Infant, Newborn; Infants; Infants (Newborn); Intellectual disabilities; Intensive care; Lung diseases; Male; MED13; Mediator Complex - genetics; Medical screening; Microcephaly; Mutation, Missense; Neonates; Optic chiasm; Optic nerve; Patient outcomes; Patients; Phenotype; Phenotypes; Proteins; Pulmonary arteries; RNA polymerase; Syndrome; Therapeutic applications; Tomography; Ultrasonic imaging; Vision disorders in children; Whole exome sequencing; Whole genome sequencing; Russia; MED13; Expanding phenotype; Whole exome sequencing; De novo variant
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-024-01857-z

Whole exome sequencing allows rapid identification of causative single nucleotide variants and short insertions/deletions in children with congenital anomalies and/or intellectual disability, which aids in accurate diagnosis, prognosis, appropriate therapeutic interventions, and family counselling. Recently, de novo variants in the MED13 gene were described in patients with an intellectual developmental disorder that included global developmental delay, mild congenital heart anomalies, and hearing and vision problems in some patients. Here we describe an infant who carried a de novo p.Pro835Ser missense variant in the MED13 gene, according to whole exome trio sequencing. He presented with congenital heart anomalies, dysmorphic features, hydrocephalic changes, hypoplastic corpus callosum, bilateral optic nerve atrophy, optic chiasm atrophy, brain stem atrophy, and overall a more severe condition compared to previously described patients. Therefore, we propose to expand the MED13-associated phenotype to include severe complications that could end up with multiple organ failure and neonatal death.