WFS1 and non-syndromic low-frequency sensorineural hearing loss: A novel mutation in a Portuguese case

Gonçalves, Ana Cláudia; Matos, Tiago; Simões-Teixeira, Helena; Machado, Marcela; Simão, Marco Alveirinho; Dias, Óscar; Andrea, Mário; Fialho, Graça; Caria, Helena

doi:10.1016/j.gene.2014.01.040

Cited by 13 publications

(5 citation statements)

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“…This protein is essential for maintaining correct levels of Ca 2+ and other charged particles necessary for hearing, and its lack of function induces apoptotic input signaling in the ER [ 16 , 17 ]. Although it remains unknown whether wolframin is expressed in the human cochlea, mutations in the WFS1 gene, such as c.511G > A (p.D171N), c.2005 T > C (p.Y669H) and c.2590G > A (p.E864K), have been identified as frequent causes of autosomal dominant low-frequency hearing loss in different ethnicities [ 18 - 20 ]. The heterozygous 3-bp deletion (c.2036_2038delAGG) identified in the present study is expected to cause the loss of the E680 codon, which might affect the three-dimensional shape or properties of the wolframin protein and consequently interfere the normal function of the wolframin tetramer.…”

Section: Discussionmentioning

confidence: 99%

Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss

et al. 2014

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BackgroundHereditary hearing loss is genetically heterogeneous, and hundreds of mutations in than 60 genes are involved in this disease. Therefore, it is difficult to identify the causative gene mutations involved. In this study, we combined targeted genomic capture and massively parallel sequencing (MPS) to address this issue.MethodsUsing targeted genomic capture and MPS, 104 genes and three microRNA regions were selected and simultaneously sequenced in 23 unrelated probands of Chinese families with nonsyndromic hearing loss. The results were validated by Sanger sequencing for all available members of the probands’ families. To analyze the possible pathogenic functional effects of the variants, three types of prediction programs (Mutation Taster, PROVEAN and SIFT) were used. A total of 195 healthy Chinese Han individuals were compared as controls to verify the novel causative mutations.ResultsOf the 23 probands, six had mutations in DFNA genes [WFS1 (n = 2), COCH, ACTG1, TMC1, and POU4F3] known to cause autosomal dominant nonsyndromic hearing loss. These included one novel in-frame indel mutation, three novel missense mutations and two reported missense mutations. Furthermore, one proband from a family with recessive DFNB carried two monoallelic mutations in the GJB2 and USH2A genes. All of these mutations co-segregated with the hearing loss phenotype in 36 affected individuals from 7 families and were predicted to be pathogenic.ConclusionsMutations in uncommon deafness genes contribute to a portion of nonsyndromic deafness cases. In the future, critical gene mutations may be accurately and quickly identified in families with hereditary hearing loss by targeted genomic capture and MPS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0311-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss

et al. 2014

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“…The WFS1 (c.449C>T; p.A150 V) identified in the present study is located in the extracellular N-terminus domain of the wolframin protein. Three other mutations in the N-terminal cytoplasmic domain of the protein, p.R161Q, p.D171N and p.K193Q, have been associated with LFSNHL [34] , [37] [45] . Other clinical features including optic atrophy have not been reported as concomitant features in families with LFSNHL.…”

Section: Discussionmentioning

confidence: 99%

Whole-Exome Sequencing to Decipher the Genetic Heterogeneity of Hearing Loss in a Chinese Family with Deaf by Deaf Mating

Yan

Zhou

et al. 2014

PLoS ONE

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Inherited deafness has been shown to have high genetic heterogeneity. For many decades, linkage analysis and candidate gene approaches have been the main tools to elucidate the genetics of hearing loss. However, this associated study design is costly, time-consuming, and unsuitable for small families. This is mainly due to the inadequate numbers of available affected individuals, locus heterogeneity, and assortative mating. Exome sequencing has now become technically feasible and a cost-effective method for detection of disease variants underlying Mendelian disorders due to the recent advances in next-generation sequencing (NGS) technologies. In the present study, we have combined both the Deafness Gene Mutation Detection Array and exome sequencing to identify deafness causative variants in a large Chinese composite family with deaf by deaf mating. The simultaneous screening of the 9 common deafness mutations using the allele-specific PCR based universal array, resulted in the identification of the 1555A>G in the mitochondrial DNA (mtDNA) 12S rRNA in affected individuals in one branch of the family. We then subjected the mutation-negative cases to exome sequencing and identified novel causative variants in the MYH14 and WFS1 genes. This report confirms the effective use of a NGS technique to detect pathogenic mutations in affected individuals who were not candidates for classical genetic studies.

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“…Так було виявлено об'єктивну хара-ктеристику вродженого дефекту слуху, виклика-ного мутованим геном WFS1 (wolframin ER transmembrane glycoprotein), білок якого в невеликій кількості утворюється тільки в завитці внутріш-нього вуха. Як встановила міжнародна група до-слідників методом суб'єктивної аудіометрії [10], цей ген відповідає за незвичний тип глухоти -зменшену здатність чути низькочастотні звуки. Припускається, що в виникненні і розвитку слуху задіяно біля 50 генів, лише 20 із яких ідентифіко-вано [11].…”

Section: акустичні прилади та системиunclassified

Method of Universal Audiological Screening of Newborns

Naida¹,

Naida²

2017

Electronics and Communications

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WFS1 and non-syndromic low-frequency sensorineural hearing loss: A novel mutation in a Portuguese case

Cited by 13 publications

References 19 publications

Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss

Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss

Whole-Exome Sequencing to Decipher the Genetic Heterogeneity of Hearing Loss in a Chinese Family with Deaf by Deaf Mating

Method of Universal Audiological Screening of Newborns

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