A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26)

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

doi:10.1136/jmg.40.12.879

Cited by 122 publications

(86 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24 It is reported that ACTG-1 is expressed at very high level in DN and has been tested to be associated with various diseases, such as neoplasms, hearing loss and kidney disease. 25 In our work, ACTG-1 was found to be involved in pathways such as adherens junction, bacterial invasion of epithelial cells, dilated cardiomyopathy, which indicated the possible relations between ACTG-1 gene and the disease occurrence.…”

Section: Discussionsupporting

confidence: 54%

Bioinformatic analysis of specific genes in diabetic nephropathy

Wei

Liu

et al. 2015

Renal Failure

View full text Add to dashboard Cite

Objective: We attempt to explore the pathogenesis and specific genes with aberrant expression in diabetic nephropathy (DN). Methods: The gene expression profile of GSE1009 was downloaded from Gene Expression Omnibus database, including 3 normal function glomeruli and DN glomeruli from cadaveric donor kidneys. The differentially expressed genes (DEGs) were analyzed and the aberrant gene-related functions were predicted by informatics methods. The protein-protein interaction (PPI) networks for DEGs were constructed and the functional subnetwork was screened. Results: A total of 416 DEGs were found to be differentially expressed in DN samples comparing with normal controls, including 404 up-regulated genes and 12 downregulated genes. DEGs were involved in the process of combination to saccharides and the decline of tissue repairing ability of the organisms. The genes of VEGFA, ACTG1, HSP90AA1 had high degree in the PPI network. The main biological process of genes in the sub-network was related with cell proliferation and signal transmitting of cell membrane receptor. Conclusion: Significant nodes in PPI network provide new insights to understand the mechanism of DN. VEGFA, ACTG1 and HSP90AA1 may be the potential targets in the DN treatment.

show abstract

Section: Discussionsupporting

confidence: 54%

Bioinformatic analysis of specific genes in diabetic nephropathy

Wei

Liu

et al. 2015

Renal Failure

View full text Add to dashboard Cite

show abstract

“…Similarly, overexpression studies in vertebrate cultured cells support the notion that some actin isoforms exhibit distinct functional capacities (Schevzov et al, 1992). Finally, point mutations in the human ACTG1 ␥ actin isoform have been implicated as the causative defect in autosomal dominant, progressive hearing loss in humans (van Wijk et al, 2003). Given that the stereocilia of the inner ear contain numerous microvilli-like structures whose characteristic staircase organization and length probably play a central role in hearing (Hudspeth and Jacobs, 1979;Howard and Hudspeth, 1987), and the potential for microvilli-specialized actins described here, it is possible that ACTG1 is uniquely adapted for function in the microvilli of the inner ear.…”

Section: Act-5 Is Uniquely Specialized For Microvilli Formationmentioning

confidence: 74%

ACT-5 Is an Essential Caenorhabditis elegans Actin Required for Intestinal Microvilli Formation

MacQueen

Baggett

Perumov

et al. 2005

MBoC

View full text Add to dashboard Cite

Investigation of Caenorhabditis elegans act-5 gene function revealed that intestinal microvillus formation requires a specific actin isoform. ACT-5 is the most diverged of the five C. elegans actins, sharing only 93% identity with the other four. Green fluorescent protein reporter and immunofluorescence analysis indicated that act-5 gene expression is limited to microvillus-containing cells within the intestine and excretory systems and that ACT-5 is apically localized within intestinal cells. Animals heterozygous for a dominant act-5 mutation looked clear and thin and grew slowly. Animals homozygous for either the dominant act-5 mutation, or a recessive loss of function mutant, exhibited normal morphology and intestinal cell polarity, but died during the first larval stage. Ultrastructural analysis revealed a complete loss of intestinal microvilli in homozygous act-5 mutants. Forced expression of ACT-1 under the control of the act-5 promoter did not rescue the lethality of the act-5 mutant. Together with immuno-electron microscopy experiments that indicated ACT-5 is enriched within microvilli themselves, these results suggest a microvillus-specific function for act-5, and further, they raise the possibility that specific actins may be specialized for building microvilli and related structures.

show abstract

“…Five different HL-causing missense mutations in ACTG1 were described in four American families 8 and in one Dutch family. 9 ACTG1 encodes g-actin, which is one of six highly conserved actin proteins in human. Actin monomers polymerize to form actin filaments, which are major structural components of the cytoskeleton and which regulate cell shape, cell motility, cell contraction and cell growth.…”

Section: Introductionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26)

Cited by 122 publications

References 38 publications

Bioinformatic analysis of specific genes in diabetic nephropathy

Bioinformatic analysis of specific genes in diabetic nephropathy

ACT-5 Is an Essential Caenorhabditis elegans Actin Required for Intestinal Microvilli Formation

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

Contact Info

Product

Resources

About