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Rare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction.

Angelo Augusto M Sumalde1,2, Melissa A Scholes1,3,4, Olivia A Kalmanson1

  • 1Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Genes
|April 28, 2023
PubMed
Summary
This summary is machine-generated.

This study identified rare genetic variants in children with peripheral vertigo, linking them to inner ear development, migraine, and musculoskeletal genes. These findings may explain causes of childhood vertigo and related conditions.

Keywords:
HMX3LAMA2Meniere’s diseaseOTOP1balance disorderdizzinessrare variantsemicircular canalvertigovestibular

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Area of Science:

  • Genetics
  • Otolaryngology
  • Pediatrics

Background:

  • Vestibular dysfunction causing vertigo is uncommon in children.
  • Previous research linked genes to hearing loss and vertigo.
  • Understanding the etiology of childhood vertigo can improve patient care.

Purpose of the Study:

  • Identify rare coding variants in children with peripheral vertigo and no hearing loss.
  • Investigate variants in patients with Meniere's disease and idiopathic scoliosis.
  • Explore genetic links between vertigo, Meniere's disease, and scoliosis.

Main Methods:

  • Exome sequencing data from 5 children with vertigo, 226 patients with Meniere's disease, and 38 with scoliosis.
  • Selection of rare variants.
  • Analysis of gene variants associated with inner ear structure, migraine, and musculoskeletal phenotypes.

Main Results:

  • 17 variants in 15 genes were found in children with vertigo, implicated in migraine, musculoskeletal, and vestibular development.
  • Three genes (OTOP1, HMX3, LAMA2) have mouse models for vestibular dysfunction and HMX3/LAMA2 are expressed in human vestibular tissue.
  • Rare variants in ECM1, OTOP1, OTOP2 were found in Meniere's disease patients; OTOP1 variants linked to semicircular canal asymmetry and scoliosis in adolescents.

Conclusions:

  • Peripheral vestibular dysfunction in children may result from multiple rare variants in genes affecting inner ear structure, migraine, and musculoskeletal systems.
  • Genetic factors may underlie overlapping phenotypes like vertigo, Meniere's disease, and scoliosis.
  • Further research into these gene variants can elucidate the pathophysiology of childhood vertigo.