Whole‐exome sequencing suggests multiallelic inheritance for childhood‐onset Ménière's disease

Skarp, Sini; Kanervo, Laura; Kotimäki, Jouko; Sorri, Martti; Männikkö, Minna; Hietikko, Elina

doi:10.1111/ahg.12327

Cited by 11 publications

(9 citation statements)

References 38 publications

(45 reference statements)

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“…Another point is that vertigo onset occurred before 30 years in 44% of cases in our cohort, thus, earlier than usual in Menière's disease, where the age of symptom onset typically ranges between 30 and 70 years [23]. However, this result can match with the early onset of symptoms in genetic Menière's disease [38].…”

Section: Discussionmentioning

confidence: 50%

Investigation of Vestibular Function in Adult Patients with Gitelman Syndrome: Results of an Observational Study

Alexandru

Courbebaisse

Pajolec

et al. 2020

JCM

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Gitelman syndrome (GS) is a rare salt-losing tubulopathy caused by an inactivating mutation in the SLC12A3 gene, encoding the thiazide-sensitive sodium chloride cotransporter (NCC). Patients with GS frequently complain of vertigo, usually attributed to hypovolemia. Because NCC is also located in the endolymphatic sac, we hypothesized that patients with GS might have vestibular dysfunction. Between April 2013 and September 2016, 20 (22%) out of 90 patients followed at the reference center complained of vertigo in the absence of orthostatic hypotension. Sixteen of them were referred to an otology department for investigation of vestibular function. The vertigo was of short duration and triggered in half of them by head rotation. Seven patients (44%) had a vestibular syndrome. Vestibular syndrome was defined: (1) clinically, as nystagmus triggered by the head shaking test (n = 5); and/or (2) paraclinically, as an abnormal video head impulse test (n = 0), abnormal kinetic test (n = 4) and/or abnormal bithermal caloric test (n = 3). Five patients had associated auditory signs (tinnitus, aural fullness or hearing loss). In conclusion, we found a high frequency of vestibular disorder in GS patients suffering from vertigo, suggesting a role of NCC in the inner ear. Referent physicians of these patients should be aware of this extrarenal manifestation that requires specific investigations and treatment.

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Section: Discussionmentioning

confidence: 50%

Investigation of Vestibular Function in Adult Patients with Gitelman Syndrome: Results of an Observational Study

Alexandru

Courbebaisse

Pajolec

et al. 2020

JCM

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“…Skarp et al [40] found two heterozygous variants in HMX2 and TMEM55B, which were present in an individual and his grandfather, both affected with MD. The father of the first individual did not report any symptoms of MD, and he would be an obligate carrier of these variants, but it was not possible to validate them because he did not donate a DNA sample for the study.…”

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%

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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“…Molecular genetics in MD, however, are less well understood. The rarer familial form (6 to 9% of MD cases) is a monogenic disorder and most families have an autosomal dominant inheritance with incomplete penetrance and variable expressivity [41,54].…”

Section: Molecular Geneticsmentioning

confidence: 99%

Interpreting pendred syndrome as a foetal hydrops: Clinical and animal model evidence

Simon

Denoyelle

Beraneck

2021

VES

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BACKGROUND: Menière disease (MD) and SLC26A4 related deafness (Pendred syndrome (PS) or DFNB4) are two different inner ear disorders which present with fluctuating and progressive hearing loss, which could be a direct consequence of endolymphatic hydrops. OBJECTIVE: To present similarities between both pathologies and explore how the concept of hydrops may be applied to PS/DFNB4. METHODS: Review of the literature on MD, PS/DFNB4 and mouse model of PS/DFNB4. RESULTS: MD and PS/DFNB4 share a number of similarities such as fluctuating and progressive hearing loss, acute episodes with vertigo and tinnitus, MRI and histological evidence of endolymphatic hydrops (although with different underlying mechanisms). MD is usually diagnosed during the fourth decade of life whereas PS/DFNB4 is congenital. The PS/DFNB4 mouse models have shown that biallelic slc26a4 mutations lead to Na + and water retention in the endolymph during the perinatal period, which in turn induces degeneration of the stria vascularis and hearing loss. Crossing clinical/imagery characteristics and animal models, evidence seems to support the hypothesis of PS being a foetal hydrops. CONCLUSIONS: When understanding PS/DFNB4 as a developmental hydrops, treatments used in MD could be repositioned to PS.

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Whole‐exome sequencing suggests multiallelic inheritance for childhood‐onset Ménière's disease

Cited by 11 publications

References 38 publications

Investigation of Vestibular Function in Adult Patients with Gitelman Syndrome: Results of an Observational Study

Investigation of Vestibular Function in Adult Patients with Gitelman Syndrome: Results of an Observational Study

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

Interpreting pendred syndrome as a foetal hydrops: Clinical and animal model evidence

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