Stereocilin gene variants associated with episodic vertigo: expansion of the DFNB16 phenotype

Frykholm, Carina; Klar, Joakim; Tomanovic, Tatjana; Ameur, Adam; Dahl, Niklas

doi:10.1038/s41431-018-0256-6

Cited by 13 publications

(10 citation statements)

References 21 publications

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“…Aside from two case reports, vertigo has not been widely described in association with DFNB16 HL (11,12). In 2018, for the first time, Frykholm et al described episodic recurrent vertigo in three related individuals with STRC variants.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions

et al. 2023

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ObjectiveDeletions of STRC gene (DFNB16) account for 12% of isolated congenital mild to moderate hearing loss (HL). In mice, the stereocilin protein, encoded by STRC, is present in the vestibular kinocilium embedded in the otoconial membrane of the utricular macula. Despite this, effects on vestibular function have not been widely investigated. The aim of this study was to investigate the prevalence of benign paroxysmal positional vertigo (BPPV) in a cohort of DFNB16 patients.Study DesignObservational descriptive epidemiological study.SettingSingle-center study, in a tertiary referral center.PatientsOlder than 5 years, with a genetic diagnosis of HL related to biallelic STRC gene deletions, diagnosed between 2015 and 2021InterventionPatients or their parents were interviewed to determine whether they had experienced vertigo or episodes of BPPV.Main Outcome MeasureCriteria were at least five acute episodes of rotatory vertigo, each lasting less than 1 minute, episodes triggered by changes in specific head position, and an absence of neurological symptoms.ResultsSixty-four patients having mild (33%) to moderate (66%) HL were included. Median age was 15 years (range, 6–48 yr). Prevalence of BPPV was 39% (25 of 64). Median age of first onset was 13 years (range, 3–18 yr).ConclusionsThis study showed recurrent BPPV and early age of onset in patients with biallelic STRC gene deletions. BPPV may be associated with the HL phenotype in patients with STRC gene deletions. It is important to inform patients and families of this potential risk such that appropriate management can be proposed.

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Section: Discussionmentioning

confidence: 99%

Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions

et al. 2023

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“…Frykholm et al [39] described a family with two brothers and a first cousin with moderate, non-progressive SNHL and episodic vertigo. The two brothers shared a nonsense homozygous variant, which is chr15:43896948G>A, in the STRC gene (NM_153700.2), and the cousin had the same variant in heterozygosis inherited from the mother and a deletion of approximately 97 kb spanning the STRC gene, inherited from the father.…”

Section: Inheritance Of Snvs Associated With Fmdmentioning

confidence: 99%

“…Some SNVs in OTOG (chr11:17574758G>A, chr11:17578774G>A, chr11:17621218C>T, chr11:17632921C>T, chr11:17663747G>A and chr11:17667139G>C) [41] were reported in multiplex families with different unrelated individuals with FMD. Whereas SNVs in PRKCB [16], DPT, SEMA3D [17], COCH [38], STRC [39], HMX2, TMEM55B [40] and LSAMP [42] were only described in simplex families. Hence, it would be necessary to find new additional cases or families with these variations to support their involvement in FMD.…”

Section: Main Findings In Fmd Candidate Genesmentioning

confidence: 99%

“…The STRC gene encodes the Stereocilin protein in cochlea and vestibule; it is associated with the gelatinous membrane overlaying the vestibular kinocilia, which suggests a role of the protein in sensing balance and spatial orientation [39]. Verpy et al [54] reported the functional association between Stereocilin and OHC; moreover, they conclude that it is essential to the formation of horizontal top connectors, which maintain the cohesiveness of the mature OHC hair bundle, and are required for the tip-link turn over.…”

Section: Classification Of Genesmentioning

confidence: 99%

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Systematic Review of Sequencing Studies and Gene Expression Profiling in Familial Meniere Disease

Escalera‐Balsera

Roman‐Naranjo

Lopez-Escamez

2020

Genes

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Familial Meniere Disease (FMD) is a rare inner ear disorder characterized by episodic vertigo associated with sensorineural hearing loss, tinnitus and/or aural fullness. We conducted a systematic review to find sequencing studies segregating rare variants in FMD to obtain evidence to support candidate genes for MD. After evaluating the quality of the retrieved records, eight studies were selected to carry out a quantitative synthesis. These articles described 20 single nucleotide variants (SNVs) in 11 genes (FAM136A, DTNA, PRKCB, COCH, DPT, SEMA3D, STRC, HMX2, TMEM55B, OTOG and LSAMP), most of them in singular families—the exception being the OTOG gene. Furthermore, we analyzed the pathogenicity of each SNV and compared its allelic frequency with reference datasets to evaluate its role in the pathogenesis of FMD. By retrieving gene expression data in these genes from different databases, we could classify them according to their gene expression in neural or inner ear tissues. Finally, we evaluated the pattern of inheritance to conclude which genes show an autosomal dominant (AD) or autosomal recessive (AR) inheritance in FMD.

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“…Mutations in >100 human genes have been identified to cause non-syndromic and syndromic hearing loss ( https://hereditaryhearingloss.org/ ). Genetic disorders with only the vestibular symptoms are rare, as most genetic peripheral vestibular disorders are also associated with hearing loss 1 , and examples include DFNA9, 11, 15, and 28 2 , as well as DFNB16 3 . Both auditory and vestibular functions may be affected in patients with either Usher syndrome 4 , enlarged vestibular aqueduct syndrome 5 , or Jervell and Lange-Nielsen syndrome (JLNS) 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2

Zhang

Li³

et al. 2021

Nat Commun

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Mutations in voltage-gated potassium channel KCNE1 cause Jervell and Lange-Nielsen syndrome type 2 (JLNS2), resulting in congenital deafness and vestibular dysfunction. We conducted gene therapy by injecting viral vectors using the canalostomy approach in Kcne1−/− mice to treat both the hearing and vestibular symptoms. Results showed early treatment prevented collapse of the Reissner’s membrane and vestibular wall, retained the normal size of the semicircular canals, and prevented the degeneration of inner ear cells. In a dose-dependent manner, the treatment preserved auditory (16 out of 20 mice) and vestibular (20/20) functions in mice treated with the high-dosage for at least five months. In the low-dosage group, a subgroup of mice (13/20) showed improvements only in the vestibular functions. Results supported that highly efficient transduction is one of the key factors for achieving the efficacy and maintaining the long-term therapeutic effect. Secondary outcomes of treatment included improved birth and litter survival rates. Our results demonstrated that gene therapy via the canalostomy approach, which has been considered to be one of the more feasible delivery methods for human inner ear gene therapy, preserved auditory and vestibular functions in a dose-dependent manner in a mouse model of JLNS2.

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Stereocilin gene variants associated with episodic vertigo: expansion of the DFNB16 phenotype

Cited by 13 publications

References 21 publications

Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions

Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions

Systematic Review of Sequencing Studies and Gene Expression Profiling in Familial Meniere Disease

Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2

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