Identification and characterization of two new disease genes implicated in developmental brain diseases
Recent studies led by Dr. Raúl Estévez from the Institute of Neurosciences of the University of Barcelona, have resulted in the identification of the genes responsible for two types of brain development diseases.
On the one hand, in a collaboration with the group of Pankaj B Agrawal, from Boston Children’s Hospital, mutations have been identified in patients with defects in brain development in the CLCN3 gene, which codes for an anion exchanger of the CLC family that it is located in the endosomes. In 11 families, homozygous mutations have been identified that would cause loss of function, but also heterozygous de novo mutations. The functional analysis of some of these mutations has shown that they present an increase in activity and loss of inhibition at acidic pH. These results have been published in the American Journal of Human Genetics.
On the other hand, in a collaboration with the group of Dr. Alfons Macaya, from the Vall d’Hebron Hospital, mutations have been identified in patients with brain development problems in the CHRM1 gene, which codes for the muscarinic M1 receptor. Analysis of one of the mutations has shown that the mutated receptor has a defective activation of its signaling pathways. These data suggest that a reduction in muscarinic signaling affects brain development. These results have been published in the journal Human Mutation.
Duncan, A., Polovitskaya, M., Gaitán-Peñas, H., Bertelli, S., VanNoy, G., & Grant, P. et al. (2021). Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders. The American Journal Of Human Genetics. doi: 10.1016/j.ajhg.2021.06.003
Marcé‐Grau, A., Elorza‐Vidal, X., Pérez‐Rius, C., Ruiz‐Nel·lo, A., Sala‐Coromina, J., & Gabau, E. et al. (2021). Muscarinic Acetylcholine Receptor M1 mutations causing neurodevelopmental disorder and epilepsy. Human Mutation. doi: 10.1002/humu.24252