Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
April-2026 Volume 31 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2026 Volume 31 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Identification of a novel PLS1 heterozygous variant causing autosomal dominant non‑syndromic hearing loss

  • Authors:
    • Chenxi Yang
    • Yao Xiong
    • Dongyang Wang
    • Juanzi Shi
  • View Affiliations / Copyright

    Affiliations: Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, Shaanxi 710000, P.R. China, Translational Medicine Center, Northwest Women's and Children's Hospital, Xi'an, Shaanxi 710000, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 110
    |
    Published online on: February 12, 2026
       https://doi.org/10.3892/etm.2026.13105
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Congenital disabling hearing impairment is a prevalent sensory deficit, affecting >30,000 newborns annually in China. Non‑syndromic hearing loss (NSHL) accounts for a notable proportion of these cases, ~60% of which are attributed to genetic defects by heterogeneity. Although >120 genes have been linked to NSHL, a definitive molecular diagnosis remains elusive for approximately one‑half of the individuals undergoing genetic testing. In the present study, a Chinese family with NSHL was investigated using next‑generation sequencing of the affected members, with validation by Sanger sequencing. A novel variant was identified, namely plastin‑1 (PLS1) c.981+5G>A. Functional analysis by reverse transcription PCR revealed that this variant induces exon skipping, establishing its pathogenic mechanism. PLS1 encodes the actin‑bundling protein plastin‑1, which is highly abundant in the stereocilia of hair cells. Recent studies have implicated PLS1 in hearing loss; therefore, the present study provides direct functional validation of its pathogenicity, expanding the pathogenic variation spectrum of PLS1 and offering valuable insights into clinical diagnostic advancements and prenatal screening.
View Figures

Figure 1

Identification of a family with
non-syndromic hearing loss. (A) Pedigree of the family. The arrow
indicates the proband. Affected family members are shown in black.
(B) Results of auditory brainstem response testing at the proband's
newborn hearing screening, showing an abnormal wave in the right
ear. (C) Pure-tone hearing testing results of the proband at 250
Hz-8k Hz, showing flat or declining curves in the bilateral ears.
Pure tone averages indicate severe-to-profound hearing loss. (D)
Pure-tone hearing testing results of the proband's mother at 250
Hz-8k Hz, showing flat or declining curves in the bilateral ears.
Pure tone averages indicate severe-to-profound hearing loss. AC,
air conduction; BC, bone conduction; SF, sound field; MCL, most
comfortable level; UCL, uncomfortable level; NR, no response; AI,
asymmetry index; HL, hearing level; SPL, sound pressure level.

Figure 2

Effects of the novel splicing mutation
c.981+5G>A in PLS1. (A) Sanger sequencing results
demonstrating the presence of heterozygous PLS1
c.981+5G>A in the proband (III-1) and her affected mother
(II-1), but the absence of the variant in the healthy father
(II-2). The arrows indicate mutated bases. (B) AUGUSTUS software
results indicating that the PLS1 c.981+5G>A variant leads
to exon 9 skipping. (C) Reverse transcription PCR results showing
that the proband and her mother both present with an extra band.
(D) Sanger sequencing showing that band b is an aberrant
transcript, which presents with 93 bp less compared with the normal
band a. (E) Schematic of exon 9 skipping due to mutation
c.981+5G>A in PLS1. PLS1, plastin-1; E, exon; WT,
wildtype.

Figure 3

Mutation c.981+5G>A in PLS1
leads to the dysfunction of plastin-1. (A) Structural model of WT
and mutant (p.S297_N327del) PLS1 (yellow) interacting with ACTB
(light blue). The region at amino acid positions 297-327 is shown
in dark blue. The α-helix at amino acid positions 293-296 is shown
in orange. (B) Conservation analysis of amino acids encoded by exon
9. PLS1, plastin-1; WT, wild-type; ACTB, β-actin.

Figure 4

Schematic of plastin-1 protein.
Plastin-1 includes an N-terminal regulatory region with two EF-hand
domains. Following this, actin-binding domains 1 and 2 are present.
Each of these domains consists of two CH domains. The majority of
the currently reported mutations map in the first actin-binding
domain, except for the mutations p.E432V and p.V553D. CH,
calponin-homology.
View References

1 

Wang Q, Xiang J, Sun J, Yang Y, Guan J, Wang D, Song C, Guo L, Wang H, Chen Y, et al: Nationwide population genetic screening improves outcomes of newborn screening for hearing loss in China. Genet Med. 21:2231–2238. 2019.PubMed/NCBI View Article : Google Scholar

2 

Shearer AE, Eppsteiner RW, Booth KT, Ephraim SS, Gurrola J II, Simpson A, Black-Ziegelbein EA, Joshi S, Ravi H, Giuffre AC, et al: Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. Am J Hum Genet. 95:445–453. 2014.PubMed/NCBI View Article : Google Scholar

3 

Lieu JEC, Kenna M, Anne S and Davidson L: Hearing loss in children: A review. JAMA. 324:2195–2205. 2020.PubMed/NCBI View Article : Google Scholar

4 

Walls WD, Azaiez H and Smith RJH: Hereditary Hearing Loss. Homepage. Available: https://hereditaryhearingloss.org. Accessed on 19 February 2025.

5 

Peng AW, Salles FT, Pan B and Ricci AJ: Integrating the biophysical and molecular mechanisms of auditory hair cell mechanotransduction. Nat Commun. 2(523)2011.PubMed/NCBI View Article : Google Scholar

6 

Mogensen MM, Rzadzinska A and Steel KP: The deaf mouse mutant whirler suggests a role for whirlin in actin filament dynamics and stereocilia development. Cell Motil Cytoskeleton. 64:496–508. 2007.PubMed/NCBI View Article : Google Scholar

7 

DeRosier DJ and Tilney LG: F-actin bundles are derivatives of microvilli: What does this tell us about how bundles might form? J Cell Biol. 148:1–6. 2000.PubMed/NCBI

8 

Lin CS, Shen W, Chen ZP, Tu YH and Matsudaira P: Identification of I-plastin, a human fimbrin isoform expressed in intestine and kidney. Mol Cell Biol. 14:2457–2467. 1994.PubMed/NCBI View Article : Google Scholar

9 

Richardson GP, de Monvel JB and Petit C: How the genetics of deafness illuminates auditory physiology. Annu Rev Physiol. 73:311–334. 2011.PubMed/NCBI View Article : Google Scholar

10 

Taylor R, Bullen A, Johnson SL, Grimm-Günter EM, Rivero F, Marcotti W, Forge A and Daudet N: Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice. Hum Mol Genet. 24:37–49. 2015.PubMed/NCBI View Article : Google Scholar

11 

Krey JF, Krystofiak ES, Dumont RA, Vijayakumar S, Choi D, Rivero F, Kachar B, Jones SM and Barr-Gillespie PG: Plastin 1 widens stereocilia by transforming actin filament packing from hexagonal to liquid. J Cell Biol. 215:467–482. 2016.PubMed/NCBI View Article : Google Scholar

12 

Schrauwen I, Melegh BI, Chakchouk I, Acharya A, Nasir A, Poston A, Cornejo-Sanchez DM, Szabo Z, Karosi T, Bene J, et al: Hearing impairment locus heterogeneity and identification of PLS1 as a new autosomal dominant gene in Hungarian Roma. Eur J Hum Genet. 27:869–878. 2019.PubMed/NCBI View Article : Google Scholar

13 

Morgan A, Koboldt DC, Barrie ES, Crist ER, García García G, Mezzavilla M, Faletra F, Mihalic Mosher T, Wilson RK, Blanchet C, et al: Mutations in PLS1, encoding fimbrin, cause autosomal dominant nonsyndromic hearing loss. Hum Mutat. 40:2286–2295. 2019.PubMed/NCBI View Article : Google Scholar

14 

Diaz-Horta O, Bademci G, Tokgoz-Yilmaz S, Guo S, Zafeer F, Sineni CJ, Duman D, Farooq A and Tekin M: Novel variant p.E269K confirms causative role of PLS1 mutations in autosomal dominant hearing loss. Clin Genet. 96:575–578. 2019.PubMed/NCBI View Article : Google Scholar

15 

Xu L, Wang X, Li J, Chen L, Wang H, Xu S, Zhang Y, Li W, Yao P, Tan M, et al: A novel PLS1 c.981+1G>A variant causes autosomal-dominant hereditary hearing loss in a family. Clin Genet. 103:413–423. 2023.PubMed/NCBI View Article : Google Scholar

16 

Cai H, Bai H, Qiao S, Xue X, Shi W and Shi J: Clinical exome sequencing for carrier screening in assisted reproductive technology and sperm donation. J Assist Reprod Genet. 42:1247–1256. 2025.PubMed/NCBI View Article : Google Scholar

17 

Bolger AM, Lohse M and Usadel B: Trimmomatic: A flexible trimmer for illumina sequence data. Bioinformatics. 30:2114–2119. 2014.PubMed/NCBI View Article : Google Scholar

18 

Li H and Durbin R: Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 26:589–595. 2010.PubMed/NCBI View Article : Google Scholar

19 

Wang Z, Zhao G, Zhu Z, Wang Y, Xiang X, Zhang S, Luo T, Zhou Q, Qiu J, Tang B, et al: VarCards2: An integrated genetic and clinical database for ACMG-AMP variant-interpretation guidelines in the human whole genome. Nucleic Acids Res. 52:D1478–D1489. 2024.PubMed/NCBI View Article : Google Scholar

20 

Miller DT, Lee K, Abul-Husn NS, Amendola LM, Brothers K, Chung WK, Gollob MH, Gordon AS, Harrison SM, Hershberger RE, et al: ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 25(100866)2023.PubMed/NCBI View Article : Google Scholar

21 

Stanke M, Diekhans M, Baertsch R and Haussler D: Using native and syntenically mapped cDNA alignments to improve de novo gene finding. Bioinformatics. 24:637–644. 2008.PubMed/NCBI View Article : Google Scholar

22 

Robinson JT, Thorvaldsdóttir H, Turner D and Mesirov JP: igv.js: An embeddable JavaScript implementation of the integrative genomics viewer (IGV). Bioinformatics. 39(btac830)2023.PubMed/NCBI View Article : Google Scholar

23 

Marti-Renom MA, Stuart AC, Fiser A, Sánchez R, Melo F and Sali A: Comparative protein structure modeling of genes and genomes. Annu RevBiophys Biomol Struct. 29:291–325. 2000.PubMed/NCBI View Article : Google Scholar

24 

Oza AM, DiStefano MT, Hemphill SE, Cushman BJ, Grant AR, Siegert RK, Shen J, Chapin A, Boczek NJ, Schimmenti LA, et al: Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss. Hum Mutat. 39:1593–1613. 2018.PubMed/NCBI View Article : Google Scholar

25 

Li W, Sun J, Ling J, Li J, He C, Liu Y, Chen H, Men M, Niu Z, Deng Y, et al: ELMOD3, a novel causative gene, associated with human autosomal dominant nonsyndromic and progressive hearing loss. Hum Genet. 137:329–342. 2018.PubMed/NCBI View Article : Google Scholar

26 

Zhao Y, Zhao F, Zong L, Zhang P, Guan L, Zhang J, Wang D, Wang J, Chai W, Lan L, et al: Exome sequencing and linkage analysis identified tenascin-C (TNC) as a novel causative gene in nonsyndromic hearing loss. PLoS One. 8(e69549)2013.PubMed/NCBI View Article : Google Scholar

27 

Bañuelos S, Saraste M and Djinović Carugo K: Structural comparisons of calponin homology domains: Implications for actin binding. Structure. 6:1419–1431. 1998.PubMed/NCBI View Article : Google Scholar

28 

de Arruda MV, Watson S, Lin CS, Leavitt J and Matsudaira P: Fimbrin is a homologue of the cytoplasmic phosphoprotein plastin and has domains homologous with calmodulin and actin gelation proteins. J Cell Biol. 111:1069–1079. 1990.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yang C, Xiong Y, Wang D and Shi J: Identification of a novel <em>PLS1</em> heterozygous variant causing autosomal dominant non‑syndromic hearing loss. Exp Ther Med 31: 110, 2026.
APA
Yang, C., Xiong, Y., Wang, D., & Shi, J. (2026). Identification of a novel <em>PLS1</em> heterozygous variant causing autosomal dominant non‑syndromic hearing loss. Experimental and Therapeutic Medicine, 31, 110. https://doi.org/10.3892/etm.2026.13105
MLA
Yang, C., Xiong, Y., Wang, D., Shi, J."Identification of a novel <em>PLS1</em> heterozygous variant causing autosomal dominant non‑syndromic hearing loss". Experimental and Therapeutic Medicine 31.4 (2026): 110.
Chicago
Yang, C., Xiong, Y., Wang, D., Shi, J."Identification of a novel <em>PLS1</em> heterozygous variant causing autosomal dominant non‑syndromic hearing loss". Experimental and Therapeutic Medicine 31, no. 4 (2026): 110. https://doi.org/10.3892/etm.2026.13105
Copy and paste a formatted citation
x
Spandidos Publications style
Yang C, Xiong Y, Wang D and Shi J: Identification of a novel <em>PLS1</em> heterozygous variant causing autosomal dominant non‑syndromic hearing loss. Exp Ther Med 31: 110, 2026.
APA
Yang, C., Xiong, Y., Wang, D., & Shi, J. (2026). Identification of a novel <em>PLS1</em> heterozygous variant causing autosomal dominant non‑syndromic hearing loss. Experimental and Therapeutic Medicine, 31, 110. https://doi.org/10.3892/etm.2026.13105
MLA
Yang, C., Xiong, Y., Wang, D., Shi, J."Identification of a novel <em>PLS1</em> heterozygous variant causing autosomal dominant non‑syndromic hearing loss". Experimental and Therapeutic Medicine 31.4 (2026): 110.
Chicago
Yang, C., Xiong, Y., Wang, D., Shi, J."Identification of a novel <em>PLS1</em> heterozygous variant causing autosomal dominant non‑syndromic hearing loss". Experimental and Therapeutic Medicine 31, no. 4 (2026): 110. https://doi.org/10.3892/etm.2026.13105
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team