Neurogenetics & Transcriptomics News

Gabel Lab identifies molecular links between Sotos and Tatton Brown Rahman Syndromes

Co-first authors of the paper, Nicole Hamagami and Dennis Wu (Photo: Dept. of Neuroscience/WUSM)

Sotos Syndrome and Tatton Brown Rahman Syndrome bear striking similarities, so much so that patients with one have been misdiagnosed as having the other. Both rare diseases cause large stature and head size, also known as overgrowth, distinct facial features, a high prevelance of autism, and intellectual disability. But the two diseases have different genetic origins: Sotos is caused by variants in the NSD1 gene while TBRS involves mutations in the DNMT3A gene. Researchers have now made progress in understanding why Sotos and TBRS are so alike. The laboratory of Harrison Gabel, PhD, Associate Professor in the Department of Neuroscience at Washington University School of Medicine, reports in Molecular Cell that mutations in NSD1 and DNMT3A in mouse models lead to convergent shifts in the activity of genes within neurons.

“We saw overwhelming overlap in concordantly upregulated genes,” said Nicole Hamagami, the co-first author of the paper. “It was pretty exciting to see. It suggests there’s this overarching genetic de-repression that’s happening between these two diseases,” added Hamagami, who is a graduate student in the Gabel Lab in the medical scientist training program.

“Our study points to neuronal DNA methylation as a convergence point in TBRS, Sotos syndrome and likely additional disorders,” said Gabel. “We think this serves as a model for how to decode distinct genetic diseases with overlapping pathology.”

Read more at the Department of Neuroscience News.