Mutations in the 'TECTA' gene identified in familial Meniere's disease
El grupo MP12-Otology and Otoneurology of the ibsGRANADA led by Jose Antonio Lopez-Escamez linked to the University of Granada and the CYBER has identified a new gene associated with familial Meniere's disease (MD).
hearing and balance consist of complex processes involving thousands of genes. When the sequence of any of these genes is altered by rare mutations, these processes can be affected, causing different types of diseases with hearing loss, such as MS.
MS is a inner ear disease which is defined by episodes of recurrent vertigo, associated with noise in the ears (tinnitus) and progressive hearing loss. The familial MS is a rare disease affecting 6-7 out of 100.000 people in Spain.
In this work, published in the journal Clinical and Translational Medicine, the entire exome of 77 families with MS has been analyzed. The results have made it possible to identify mutations single nucleotide and rare deletions in the gene TECTA in 6 different families.
The Gen TECTA encodes a protein called alpha-tectorin, which is specific to the tectorial membrane and otolithic membrane of the inner ear. These membranes play a critical role in hearing and balance processes, since they are in intimate contact with the hair cells of the inner ear through the stereocilia. This contact regulates the opening of ion channels in the stereocilia and the depolarization of nerve endings. Therefore, these mutations can affect the structure of alpha-tectorin and the formation of the tectorial membrane, thereby alter sound transmission or motion detection and head acceleration.
This gene had already been related to other types of deafness and it is not the first gene associated with this disease. The genetics of familial MS is complex, having described in recent years different relationships between this disease and various genes, such as OTOG, MYO7A, HRC23, PCDH15 o ADGRV1. However, these genes have something in common: they all fulfill a important role in the hair cells of the auditory organ and the tectorial membrane, which regulates the entry of calcium and potassium ions into the cells by sending the nerve impulse.
The results of this article They seem to indicate that the origin of familial MS could be found in the proteins that unite the cilia of the auditory cells or form the tectorial and otolithic membranes.
El research group 'Otology and Otoneurology CTS495' led by Prof. López-Escámez is a international benchmark in the investigation of the genetic and immunological alterations of MS. He is currently developing several research projects financed by the Carlos III Health Institute, the Ministry of Health and Families of the Andalusian Government, the Ministry of Economic Transformation, Industry, Knowledge and Universities and the CIBERER.
The study of MS and the identification of new genes that may explain the origin of the disease can help decipher disease mechanisms, facilitating its early genetic diagnosis, as well as the development and application of new drugs for its treatment.
Graphic explanation of the study.
Reference article:
Roman-Naranjo, P., Parra-Perez, AM, Escalera-Balsera, A., Soto-Varela, A., Gallego-Martinez, A., Aran, I., Perez-Fernandez, N., Bächinger, D. , Eckhard, AH, Gonzalez-Aguado, R., Frejo, L. and Lopez-Escamez, JA (2022), Defective α-tectorin may involve tectorial membrane in familial Meniere disease. Clin. Transl. Med., 12:e829. https://doi.org/10.1002/ctm2.829