Kleefstra Syndrome (KS) is a rare monogenetic syndrome, caused by haploinsufficiency of the euchromatic histone methyl transferase 1 (EHMT1) gene, an important regulator of neurodevelopment. The clinical features of KS include intellectual disability, autistic behavior and gastrointestinal problems. The gut microbiota, an important modifier of the gut-brain-axis, may constitute an unexplored mechanism underlying clinical KS variation. We investigated the gut microbiota composition of 23 individuals with KS (patients) and 40 of their family members, to test whether (1) variation in the gut microbiota associates with KS diagnosis and (2) variation within the gut microbiota relates with KS syndrome symptoms. Both alpha and beta diversity of patients were different from their family members. Genus Coprococcus 3 was lower in abundance in patients compared to family members. Moreover, abundance of genus Merdibacter was lower in patients versus family members, but only in participants reporting intestinal complaints. Within the patient group, behavioral problems explained 7% of beta diversity variance. Also, within this group, we detected higher levels of Atopobiaceae – uncultured and Ruminococcaceae Subdoligranulum associated with higher symptom severity. These significant signatures in the gut microbiota composition in patients with KS suggest that microbiota differences are part of the KS phenotype.
The role of the gut microbiota in patients with Kleefstra syndrome
Mirjam Bloemendaal, Priscilla Vlaming, Anneke de Boer, Karlijn Vermeulen-Kalk, Arianne Bouman, Tjitske Kleefstra, Alejandro Arias Vasquez
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics