A novel mutation of TMPRSS3 related to milder auditory phenotype in Korean postlingual deafness: a possible future implication for a personalized auditory rehabilitation

Chung, Juyong; Park, Sang Min; Chang, Sun O; Chung, Taesu; Lee, Kyoung Yeul; Kim, Ah Reum; Park, Joo Hyun; Kim, Veronica; Park, Woong-Yang; Oh, Seung-Ha; Kim, Dongsup; Park, Woo Jin; Choi, Byung Yoon

doi:10.1007/s00109-014-1128-3

Cited by 36 publications

(53 citation statements)

References 23 publications

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“…Abrupt down-sloping, ski slope-type hearing loss, as occurred in subject SB114-206, caught our attention (Figure 1a) because alterations in TMPRSS3, a serine protease, are also known to cause progressive ski slope-type hearing loss. 22,23 The fact that alterations in both protease and protease inhibitors cause ski slope-type SNHL may imply that highfrequency hearing is more vulnerable to imbalance between the activities of proteases and protease inhibitors. In this study we also investigated the digenic inheritance of moderate SNHL involving two Usher syndrome type II (USH2)-related genes, GPR98 and PDZD7.…”

Section: Genetics In Medicine | Volume 17 | Number 11 | November 2015mentioning

confidence: 99%

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim

Park

et al. 2015

Genetics in Medicine

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Purpose: This study was designed to delineate genetic contributions, if any, to sporadic forms of mild to moderate sensorineural hearing loss (SNHL) not related to GJB2 mutations (DFNB1) in a pediatric population. Methods:We recruited 11 non-DFNB1 simplex cases of mild to moderate SNHL in children. We applied whole-exome sequencing to all 11 probands. We used a filtering strategy assuming that de novo variants of known autosomal dominant (AD) deafness genes, biallelic mutations in autosomal recessive (AR) genes, monoallelic mutations in X chromosome genes for males, and digenic inheritance could be associated. Candidate variants first were prioritized with allele frequency in public databases and confirmed by a phase or a segregation test in each family. Additional information from the literature or public databases was used to identify strong candidate variants.Results: Strong candidate variants were detected in 5 of 11 probands (45.4%). A diverse mode of inheritance implicated the sporadic occurrence of the phenotype. AR mutations in OTOGL and SERPINB6 and digenic inheritance involving two deafness genes, GPR98 and PDZ7, were detected. A de novo AD mutation also was detected in TECTA and MYH14. No syndromic feature was detected in individuals with GPR98/PDZ7 or MYH14 variants in our cohort at this moment. Conclusion:Mild to moderate pediatric SNHL, even if sporadic, features a strong genetic etiology and can manifest via diverse modes of inheritance. In addition, a multidisciplinary approach should be used for a correct diagnosis. Genet Med advance online publication 26 February 2015

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Section: Genetics In Medicine | Volume 17 | Number 11 | November 2015mentioning

confidence: 99%

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim

Park

et al. 2015

Genetics in Medicine

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“…Mutations in TMPRSS3 gene encoding transmembrane serine protease are associated with two ARNSHL phenotypes, DFNB8 with childhood onset and DFNB10 where hearing loss is congenital and severe [7]. TMPRSS3 mutations are predicted to account for \1 % of ARNSHL in Caucasians [8] but are more frequent among Pakistani (1.8 %) [9], Tunisian (5 %) [10], Korean (5.9 %) [11] and especially Turkish patients (12 %) [12].…”

Section: Introductionmentioning

confidence: 99%

TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss

Battelino

Klančar

Kovač

et al. 2015

Eur Arch Otorhinolaryngol

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Nonsyndromic genetic deafness is highly heterogeneous in its clinical presentation, pattern of inheritance and underlying genetic causes. Mutations in TMPRSS3 gene encoding transmembrane serine protease account for <1 % of autosomal recessive nonsyndromic hearing loss (ARNSHL) in Caucasians. Targeted next generation sequencing in the index family with profound deaf parents and a son, and Sanger sequencing of selected TMPRSS3 gene regions in a cohort of thirty-five patients with suspected ARNSHL was adopted. A son and his mother in the index family were homozygous for TMPRSS3 c.208delC (p.His70Thrfs*19) variant. Father was digenic compound heterozygote for the same variant and common GJB2 c.35delG variant. Three additional patients from the ARNSHL cohort were homozygous for TMPRSS3 c.208delC. TMPRSS3 defects seem to be an important cause of ARNSHL in Slovenia resulting in uniform phenotype with profound congenital hearing loss, and satisfactory hearing and speech recognition outcome after cochlear implantation. Consequently, TMPRSS3 gene analysis should be included in the first tier of genetic investigations of ARNSHL along with GJB2 and GJB6 genes.

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“…The variant p.V37I is usually responsible for mild-to-moderate and later-onset hearing loss and its carrier frequency is very high (up to 18.2%) among Korean with mild or slight hearing loss [3, 13, 41]. Moreover, the p.A306T mutation of TMPRSS3 , which has been reported to be a founder allele in Koreans, can be associated with the postlingual ski slope type of progressive SNHL [20]. Detection of p.A306T in TMPRSS3 using this kit can potentially provide surgeons with valuable information regarding how and when to rehabilitate SNHL, as the rapidity of SNHL progression related to TMPRSS3 is likely to depend on the type of the mutant allele of TMPRSS3 in a trans configuration with p.A306T [20, 42].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the p.A306T mutation of TMPRSS3 , which has been reported to be a founder allele in Koreans, can be associated with the postlingual ski slope type of progressive SNHL [20]. Detection of p.A306T in TMPRSS3 using this kit can potentially provide surgeons with valuable information regarding how and when to rehabilitate SNHL, as the rapidity of SNHL progression related to TMPRSS3 is likely to depend on the type of the mutant allele of TMPRSS3 in a trans configuration with p.A306T [20, 42]. The residual low frequency hearing would aggravate very rapidly or be maintained for scores of years, depending on the combination of the 2 mutant alleles.…”

Section: Discussionmentioning

confidence: 99%

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Establishment of a Flexible Real-Time Polymerase Chain Reaction-Based Platform for Detecting Prevalent Deafness Mutations Associated with Variable Degree of Sensorineural Hearing Loss in Koreans

Han

Kim

et al. 2016

PLoS ONE

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Many cutting-edge technologies based on next-generation sequencing (NGS) have been employed to identify candidate variants responsible for sensorineural hearing loss (SNHL). However, these methods have limitations preventing their wide clinical use for primary screening, in that they remain costly and it is not always suitable to analyze massive amounts of data. Several different DNA chips have been developed for screening prevalent mutations at a lower cost. However, most of these platforms do not offer the flexibility to add or remove target mutations, thereby limiting their wider use in a field that requires frequent updates. Therefore, we aimed to establish a simpler and more flexible molecular diagnostic platform based on ethnicity-specific mutation spectrums of SNHL, which would enable bypassing unnecessary filtering steps in a substantial portion of cases. In addition, we expanded the screening platform to cover varying degrees of SNHL. With this aim, we selected 11 variants of 5 genes (GJB2, SLC26A4, MTRNR1, TMPRSS3, and CDH23) showing high prevalence with varying degrees in Koreans and developed the U-TOP™ HL Genotyping Kit, a real-time PCR-based method using the MeltingArray technique and peptide nucleic acid probes. The results of 271 DNA samples with wild type sequences or mutations in homo- or heterozygote form were compared between the U-TOP™ HL Genotyping Kit and Sanger sequencing. The positive and negative predictive values were 100%, and this method showed perfect agreement with Sanger sequencing, with a Kappa value of 1.00. The U-TOP™ HL Genotyping Kit showed excellent performance in detecting varying degrees and phenotypes of SNHL mutations in both homozygote and heterozygote forms, which are highly prevalent in the Korean population. This platform will serve as a useful and cost-effective first-line screening tool for varying degrees of genetic SNHL and facilitate genome-based personalized hearing rehabilitation for the Korean population.

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A novel mutation of TMPRSS3 related to milder auditory phenotype in Korean postlingual deafness: a possible future implication for a personalized auditory rehabilitation

Cited by 36 publications

References 23 publications

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss

Establishment of a Flexible Real-Time Polymerase Chain Reaction-Based Platform for Detecting Prevalent Deafness Mutations Associated with Variable Degree of Sensorineural Hearing Loss in Koreans

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