Rare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction
| Autor: | Angelo Augusto M. Sumalde, Melissa A. Scholes, Olivia A. Kalmanson, Elizabeth A. Terhune, Lidia Frejo, Cambria I. Wethey, Pablo Roman-Naranjo, Patrick M. Carry, Samuel P. Gubbels, Jose A. Lopez-Escamez, Nancy Hadley-Miller, Regie Lyn P. Santos-Cortez |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Genes; Volume 14; Issue 4; Pages: 831 |
| ISSN: | 2073-4425 |
| DOI: | 10.3390/genes14040831 |
| Popis: | The following are available online at https://www.mdpi.com/article/ 10.3390/genes14040831/s1 A.A.M.S. received a scholarship from the Philippine Council for Health and Research Development of the Department of Science and Technology (PCHRD-DOST) under the Research Enrichment (Sandwich) Grant of the Accelerated Science and Technology Human Resource Devel- opment Program. O.A.K. was supported by the US National Institutes of Health (NIH)—National Institute on Deafness and Other Communication Disorders (NIDCD) grant T32 DC012280 (to Sue C. Kinnamon and Herman A. Jenkins). This work was supported by the NIH through the NIDCD grants R01 DC019642 (to R.L.P.S.-C. and Ivana V. Yang) and R01 DC013912 (to S.P.G.); and the National Insti- tute of Arthritis and Musculoskeletal and Skin Diseases grant R01 AR068292 (to N.H.-M.). Funding was also provided by Junta de Andalucia, grant Retos en Investigacion PY20_00303 (to J.A.L.-E.). Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo. This study aimed to identify rare, coding variants in children with peripheral vertigo but no hearing loss, and in patients with potentially overlapping phenotypes, namely, Meniere’s disease or idiopathic scoliosis. Rare variants were selected from the exome sequence data of 5 American children with vertigo, 226 Spanish patients with Meniere’s disease, and 38 European–American probands with scoliosis. In children with vertigo, 17 variants were found in 15 genes involved in migraine, musculoskeletal phenotypes, and vestibular development. Three genes, OTOP1, HMX3, and LAMA2, have knockout mouse models for vestibular dysfunction. Moreover, HMX3 and LAMA2 were expressed in human vestibular tissues. Rare variants within ECM1, OTOP1, and OTOP2 were each identified in three adult patients with Meniere’s disease. Additionally, an OTOP1 variant was identified in 11 adolescents with lateral semicircular canal asymmetry, 10 of whom have scoliosis. We hypothesize that peripheral vestibular dysfunction in children may be due to multiple rare variants within genes that are involved in the inner ear structure, migraine, and musculoskeletal disease. Philippine Council for Health and Research Development of the Department of Science and Technology (PCHRD-DOST) under the Research Enrichment (Sandwich) Grant of the Accelerated Science and Technology Human Resource Development Program US National Institutes of Health (NIH)-National Institute on Deafness and Other Communication Disorders (NIDCD) T32 DC012280 NIH through the NIDCD R01 DC019642, R01 DC013912 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R01 AR068292 Junta de Andalucia PY20_00303 |
| Databáze: | OpenAIRE |
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