New genes associated with familial Meniere's disease, an inner ear disorder that causes dizziness and tinnitus, are identified
This disease has a hereditary component that has been shown in family aggregation studies, and approximately 10% of patients have one or more affected relatives
A team of scientists from the University of Granada and the Center for Genomics and Oncology Research (Genyo), led by Pablo Roman-Naranjo and Jose Antonio Lopez-Escamez. Researcher in charge of the Biosanitary Research Institute of Granada (ibs.GRANADA), has identified new genes associated with familial Meniere's disease.
Meniere's disease is a disorder of the inner ear that is defined by episodes of recurrent vertigo and noise in the ears (tinnitus) leading to progressive hearing loss.
This disease has a hereditary component that has been shown in family aggregation studies, and approximately 10% of patients have one or more affected relatives. In this work published in the journal Hearing Research, a total of 62 families with this disease have been analyzed, most of them from Spain. The results of this study indicate the existence of a relationship between familial Meniere's disease and various ear genes, the main candidate being the MYO7A gene, which encodes a protein called myosin VIIa, which is specific to inner ear hair cells.
The function of the ear depends on thousands of genes. When these genes are altered by rare mutations, the ability to maintain balance and hearing can decrease. In the case of Meniere's disease, the researchers in this study propose a model of digenic inheritance, where rare mutations are necessary in at least 2 genes.
The origin of the disease in some of the families seems to be due to rare mutations in the MYO7A gene, together with mutations in other genes, such as CDH23, PCDH15 or ADGRV1, genes with which MYO7A interacts. This hypothesis is based on the results obtained in the study: 9 of the families included had rare mutations in these genes.
As pointed out in the article, these genes are expressed in a specific area of the ear: the stereocilia of the neurosensory cells of the inner ear. These cells are responsible for the transmission of sound in the organ of Corti, as well as the perception of acceleration in the posterior labyrinth, sending nerve impulses to the central nervous system. The stereocilia are found grouped in each of these cells. According to the authors, mutations in MYO7A and other genes would cause alterations in several proteins that hold stereocilia together, ultimately causing hearing loss and vertigo:
“We suggest that rare mutations in the MYO7A gene, alone or combined with other mutations in genes that interact with MYO7A, would cause alterations in the morphostructure of the stereocilia and a loss of cohesion between them, with the abnormal opening of the mechanotransduction complex, which it is located in the cilia and finally there is a loss of hearing and / or vertigo. The MYO7A gene has been associated with familial sensorineural hearing loss or retinitis pigmentosa, another rare disease that causes blindness "
The research group 'Otology and Otoneurology CTS495', led by López-Escámez, coordinates genomic studies in collaboration with more than 15 hospitals in Spain, Italy and Switzerland and participates in several research projects on Meniere's disease funded by the Institute Carlos III Health Department (PI20-1126), the Department of Health and Families (PI027-2020) and the Department of Economic Transformation, Industry, Knowledge and Universities (PI20-00303),
The study of Meniere's disease and the identification of new genes that can explain the origin of the disease can help to decipher the mechanisms of the disease, facilitating its early genetic diagnosis, as well as the development and application of new drugs for your treatment.
Bibliographic reference:
Roman-Naranjo P, Moleon MDC, Aran I, et al. Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease. Hear Res. 2021; 409: 108329. doi: 10.1016 / j.heares.2021.108329
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