A Dutch Family With Hearing Loss Linked to the DFNA20/26 Locus

Kemperman, Martijn H; Leenheer, Els De; Huygen, P.L.M.; Wijk, Erwin van; Duijnhoven, Gerard van; Cremers, Frans P.M.; Kremer, Hannie; Cremers, C.W.R.J.

doi:10.1001/archotol.130.3.281

Cited by 13 publications

(16 citation statements)

References 24 publications

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“…However, despite similarities between presbyacusis and g-actinrelated hearing abnormality, the age of onset of g-actinrelated hearing abnormality was 30 years earlier than presbyacusis, the rate of progression was faster and the degree to which mid-frequencies became affected with increasing age was much more pronounced. 29 Moreover, the speech recognition was found to be better in DFNA20/ 26 individuals than in individuals with presbyacusis. 29 These discrepancies may indicate that ACTG1 missense mutations may not be involved in presbyacusis to any significant extent.…”

Section: Discussionmentioning

confidence: 95%

“…29 Moreover, the speech recognition was found to be better in DFNA20/ 26 individuals than in individuals with presbyacusis. 29 These discrepancies may indicate that ACTG1 missense mutations may not be involved in presbyacusis to any significant extent.…”

Section: Discussionmentioning

confidence: 95%

“…The maximum rate of progression occurred between 10 and 35 years of age with a progression rate of 3 -8 dB/year, and by age 30 -50 years the final degree of residual hearing was reached. 29 As ACTG1 missense mutations appear to sensitize hair cells to age-dependent degeneration, it can be speculated that such mutations may be involved in the widely occurring HL of the elderly, called presbyacusis. However, despite similarities between presbyacusis and g-actinrelated hearing abnormality, the age of onset of g-actinrelated hearing abnormality was 30 years earlier than presbyacusis, the rate of progression was faster and the degree to which mid-frequencies became affected with increasing age was much more pronounced.…”

Section: Discussionmentioning

confidence: 99%

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A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment

et al. 2006

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The c-actin gene (ACTG1) encodes a major cytoskeletal protein of the sensory hair cells of the cochlea. Recently, mutations in ACTG1 were found to cause autosomal dominant, progressive, sensorineural hearing impairment linked to the DFNA20/26 locus on chromosome 17q25.3 in four American families and in one Dutch family. We report here the linkage of autosomal dominant, progressive, sensorineural hearing impairment in a large Norwegian family to the DFNA20/26 locus. Sequencing of ACTG1 identified a novel missense mutation (c.1109T4C; p.V370A) segregating with the hearing loss. Functional analysis in yeast showed that the p.V370A mutation restricts cell growth at elevated temperature or under hyperosmolar stress. Molecular modelling suggested that the p.V370A mutation modestly alters a site for protein -protein interaction in c-actin and thereby modestly alters c-actin-based cytoskeletal structures. Nineteen Norwegian and Danish families with autosomal, dominant hearing impairment were analyzed for mutations in ACTG1 by sequencing, but no disease-associated mutations were identified. Finally, a longterm follow-up of the hearing loss progression associated with the p.V370A mutation in ACTG1 is provided. The present study expands our understanding of the genotype -phenotype relationship of this deafness gene and provides a sensitive and simple functional assay for missense mutations in this gene, which may assist future molecular diagnosis of autosomal-dominant hearing impairment. Finally, the present results do not indicate that mutations in ACTG1 are a frequent cause of autosomal-dominant postlingual sensorineural hearing impairment in Norway nor Denmark.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment

et al. 2006

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“…Fast deterioration of hearing in the first decades of life, as seen in family W08-1701, has been reported previously for patients with mutations in a number of genes, including ACTG1 (MIM 102560) encoding the cytoskeletal g-1-actin. 33,34 Interestingly, this is thought to be the major cytoskeletal actin in costameres. 35 In conclusion, this study identifies SMPX as a gene in which variation is associated with X-linked deafness and illustrates that NGS is instrumental in the efficient identification of disease-causing variants in unexpected genes.…”

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confidence: 99%

Next-Generation Sequencing Identifies Mutations of SMPX, which Encodes the Small Muscle Protein, X-Linked, as a Cause of Progressive Hearing Impairment

Schraders

Haas

Weegerink

et al. 2011

The American Journal of Human Genetics

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In a Dutch family with an X-linked postlingual progressive hearing impairment, a critical linkage interval was determined to span a region of 12.9 Mb flanked by the markers DXS7108 and DXS7110. This interval overlaps with the previously described DFNX4 locus and contains 75 annotated genes. Subsequent next-generation sequencing (NGS) detected one variant within the linkage interval, a nonsense mutation in SMPX. SMPX encodes the small muscle protein, X-linked (SMPX). Further screening was performed on 26 index patients from small families for which X-linked inheritance of nonsyndromic hearing impairment (NSHI) was not excluded. We detected a frameshift mutation in SMPX in one of the patients. Segregation analysis of both mutations in the families in whom they were found revealed that the mutations cosegregated with hearing impairment. Although we show that SMPX is expressed in many different organs, including the human inner ear, no obvious symptoms other than hearing impairment were observed in the patients. SMPX had previously been demonstrated to be specifically expressed in striated muscle and, therefore, seemed an unlikely candidate gene for hearing impairment. We hypothesize that SMPX functions in inner ear development and/or maintenance in the IGF-1 pathway, the integrin pathway through Rac1, or both.

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“…We compared the present impairment-performance plot (bottom panel of Fig. 4) to similar plots for presbyacusis, DFNA2, DFNA5, DFNA9, and DFNA20/26 patients previously evaluated at our clinic (19). We found that the speech recognition performance in relation with the level of impairment was relatively good in our present MIDD patients.…”

Section: Discussionmentioning

confidence: 67%

Progressive Sensorineural Hearing Impairment in Maternally Inherited Diabetes Mellitus and Deafness (MIDD)

Hendrickx¹,

Mudde²,

Hart³

et al. 2006

Otology &Amp; Neurotology

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A Dutch Family With Hearing Loss Linked to the DFNA20/26 Locus

Cited by 13 publications

References 24 publications

A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment

A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment

Next-Generation Sequencing Identifies Mutations of SMPX, which Encodes the Small Muscle Protein, X-Linked, as a Cause of Progressive Hearing Impairment

Progressive Sensorineural Hearing Impairment in Maternally Inherited Diabetes Mellitus and Deafness (MIDD)

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