Mutation in the <i>COCH</i> gene is associated with superior semicircular canal dehiscence

Hildebrand, Michael S.; Tack, Dylan; DeLuca, Adam P.; Hur, In Ae; Rybroek, Jana M. Van; McMordie, Sarah J.; Muilenburg, Ann; Hoskinson, David P.; Camp, Guy Van; Pensak, Myles L.; Storper, Ian S.; Huygen, P.L.M.; Casavant, Thomas L.; Smith, Richard J.H.

doi:10.1002/ajmg.a.32618

Cited by 48 publications

(44 citation statements)

References 34 publications

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“…Sample 1 was from a family segregating ADNSHL. Of three candidate variants, the known hearing loss mutation in COCH (c.151C > T, p.P51S, rs28938175; DFNA9) was the only variant that segregated with the phenotype in this family (16). In samples 2 and 3 (biological replicates), the only candidate variant determined in each sample was the known deafness mutation in GJB2 (c.109G > A, p.V37I; DFNB1) (17).…”

Section: Resultsmentioning

confidence: 88%

“…NSHL, nonsyndromic hearing loss; ADNSHL, autosomal dominant nonsyndromic hearing loss; ARNSHL, autosomal recessive nonsyndromic hearing loss; Pos Ctrl, positive control; RO-segregation, mutation ruled out by segregation analysis; ROcontrols, mutation ruled out by controls analysis. *Previously reported (16 We paired NimbleGen solid phase sequence capture with 454 GS FLX pyrosequencing (NimbleGen-454 method) and SureSelect solution-based sequence capture with Illumina GAII sequencing (SureSelect-Illumina method) to determine the efficacy of these approaches for clinical diagnostics. Samples 1 and 2 were sequenced using both the NimbleGen-454 and SureSelectIllumina to provide direct comparison of these methods, whereas samples 3-10 were examined only using SureSelect-Illumina.…”

Section: Resultsmentioning

confidence: 99%

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Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing

Shearer

DeLuca²,

Hildebrand³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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312

302

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The extreme genetic heterogeneity of nonsyndromic hearing loss (NSHL) makes genetic diagnosis expensive and time consuming using available methods. To assess the feasibility of targetenrichment and massively parallel sequencing technologies to interrogate all exons of all genes implicated in NSHL, we tested nine patients diagnosed with hearing loss. Solid-phase (NimbleGen) or solution-based (SureSelect) sequence capture, followed by 454 or Illumina sequencing, respectively, were compared. Sequencing reads were mapped using GSMAPPER, BFAST, and BOWTIE, and pathogenic variants were identified using a custom-variant calling and annotation pipeline (ASAP) that incorporates publicly available in silico pathogenicity prediction tools (SIFT, BLOSUM, Polyphen2, and Align-GVGD). Samples included one negative control, three positive controls (one biological replicate), and six unknowns (10 samples total), in which we genotyped 605 single nucleotide polymorphisms (SNPs) by Sanger sequencing to measure sensitivity and specificity for SureSelect-Illumina and NimbleGen-454 methods at saturating sequence coverage. Causative mutations were identified in the positive controls but not in the negative control. In five of six idiopathic hearing loss patients we identified the pathogenic mutation. Massively parallel sequencing technologies provide sensitivity, specificity, and reproducibility at levels sufficient to perform genetic diagnosis of hearing loss.deafness | genomics | Usher syndrome | diagnostics | next-generation sequencing H ereditary sensorineural hearing loss (SNHL) is the most common sensory impairment in humans (1, 2). In developed countries, two-thirds of prelingual-onset SNHL is estimated to have a genetic etiology, of which ∼70% is nonsyndromic hearing loss (NSHL). Eighty percent of NSHL is autosomal recessive nonsyndromic hearing loss (ARNSHL), ∼20% is autosomal dominant (AD), and the remainder is composed of X-linked and mitochondrial forms (1, 3). To date, 134 deafness loci have been identified, and 32 recessive (DFNB), 23 dominant (DFNA) and 2 X-linked (DFNX) genes have been cloned; 8 genes are associated with both ARNSHL and ADNSHL (4).Establishing a genetic diagnosis of NSHL is a critical component of the clinical evaluation of deaf and hard-of-hearing persons and their families. If a genetic cause of hearing loss is determined, it is possible to provide families with prognostic information, recurrence risks, and improved habilitation options. For persons diagnosed with Usher syndrome, preventative measures including sunlight protection and vitamin therapy can be implemented to minimize the rate of progression of retinitis pigmentosa (5). Most current genetic testing strategies for NSHL rely on a gene-specific Sanger sequencing approach. Because mutations in a single gene, GJB2 (DFNB1), account for up to 50% of ARNSHL in many world populations (6), this approach has changed the evaluation of patients with presumed ARNSHL. However, the mutation frequency in other genes in persons with NSHL in outbred populat...

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Section: Resultsmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing

Shearer

DeLuca²,

Hildebrand³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

312

302

View full text Add to dashboard Cite

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“…The presence of SSCD has been previously reported in a single member of a kinship with a COCH mutation [Hildebrand et al, 2009]. …”

Section: Possible Relevance Of Osteoclastic Activity To Sscdmentioning

confidence: 99%

Evidence of Osteoclastic Activity in the Human Temporal Bone

Kamakura

Nadol²

2017

Audiol Neurotol

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Bone remodeling within the otic capsule has been reported to be inhibited especially at or near the cochlea, except under some pathological conditions such as otosclerosis, Paget's disease, or mastoiditis, when bone remodeling can occur. Microcavitations found in periosteal and endosteal layers of human temporal bone specimens without otosclerosis, Paget's disease, or inflammation as reported in the current study are consistent with osteoclastic bone resorption. Thirty-three temporal bones from 33 patients were prepared for light microscopy and classified into 4 groups: histologically proven dehiscence of the superior semicircular canal (SSCD) (n = 3, group 1), age 20 years or younger (n = 10, group 2), age 90 years or older and with otosclerosis (n = 10, group 3), and age 90 years or older without otosclerosis (n = 10, group 4). Microcavitation was seen at 7 anatomic locations in the temporal bone in all 4 groups, but not in the cochlea or vestibule. Microcavitation within the temporal bone is likely due to osteoclastic activity, and it is seen in both young and old patients, patients with and without otosclerosis, and in cases with SSCD.

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“…Hildebrand et al 26 interestingly found an association between DFNA9 (P51S) and superior semicircular canal dehiscence in 1 patient. It might be worthwhile to subject DFNA9 patients to high-resolution temporal bone computed tomographic scanning, because the symptoms of canal dehiscence can be partially or fully corrected with surgery.…”

Section: Discussionmentioning

confidence: 95%