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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
July-2025 Volume 32 Issue 1

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
July-2025 Volume 32 Issue 1

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_Data1.pdf
    • Supplementary_Data2.pdf
Article Open Access

Novel compound heterozygous mutation in DNAH9 causes complex congenital heart disease

  • Authors:
    • Xiao Liu
    • Jing‑Lin Zhou
    • Cheng-Ying Yang
    • Hai-Yan Zhou
    • Wen-Bin He
    • Jing Yang
  • View Affiliations / Copyright

    Affiliations: Department of Maternity, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China, Department of Genetics, Hunan Guangxiu Hospital Affiliated with Hunan Normal University, Hunan Normal University Health Science Centre, Changsha, Hunan 410017, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 198
    |
    Published online on: May 12, 2025
       https://doi.org/10.3892/mmr.2025.13563
  • 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 heart disease (CHD) is the most common birth defect, affecting 2‑8% of newborns, with a marked impact on neonatal health. In the present study, the parents of a fetus diagnosed with CHD were recruited to investigate the genetic causes of this condition. Whole exome sequencing was conducted on tissue obtained from the fetus. A compound heterozygous mutation in the dynein axonemal heavy chain 9 (DNAH9) gene, comprising c.11176C>T (p.Arg3726Trp) and c.3743+1G>T, was identified. The c.11176C>T mutation has been previously reported as likely pathogenic, and c.3743+1G>T is a novel mutation. Sanger sequencing was employed for pedigree analysis. In addition, bioinformatics analyses were performed to predict the pathogenicity of the identified mutations, while in silico and minigene analyses were conducted to examine the splicing patterns associated with the splicing mutation. Software predictions and minigene analysis revealed that the c.3743+1G>T mutation leads to abnormal splicing. According to the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, the two identified DNAH9 mutations were classified as likely pathogenic. The present study identified the pathogenic variants in the affected family and expanded the mutation spectrum of the DNAH9 gene. It also provided a foundation for genetic counseling and reproductive intervention.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Hoffman JI, Kaplan S and Liberthson RR: Prevalence of congenital heart disease. Am Heart J. 147:425–439. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Lambrechts D, Devriendt K, Driscoll DA, Goldmuntz E, Gewillig M, Vlietinck R, Collen D and Carmeliet P: Low expression VEGF haplotype increases the risk for tetralogy of Fallot: A family-based association study. J Med Genet. 42:519–522. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Kalisch-Smith JI, Ved N and Sparrow DB: Environmental risk factors for congenital heart disease. Cold Spring Harb Perspect Biol. 12:a0372342020. View Article : Google Scholar : PubMed/NCBI

4 

Williams K, Carson J and Lo C: Genetics of congenital heart disease. Biomolecules. 9:8792019. View Article : Google Scholar : PubMed/NCBI

5 

Van der Bom T, Zomer AC, Zwinderman AH, Meijboom FJ, Bouma BJ and Mulder BJ: The changing epidemiology of congenital heart disease. Nat Rev Cardiol. 8:50–60. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Shaikh Qureshi WM and Hentges KE: Functions of cilia in cardiac development and disease. Ann Hum Genet. 88:4–26. 2024. View Article : Google Scholar : PubMed/NCBI

7 

Yang X, Wang Q, Li T, Zhou Y, Gao J, Ma W, Zhao N, Liu X, Ai Z, Cheng SY, et al: A splicing variant in EFCAB7 hinders ciliary transport and disrupts cardiac development. J Biol Chem. 301:1082492025. View Article : Google Scholar : PubMed/NCBI

8 

Saric N and Ishibashi N: The role of primary cilia in congenital heart defect-associated neurological impairments. Front Genet. 15:14602282024. View Article : Google Scholar : PubMed/NCBI

9 

Tang D, Sha Y, Gao Y, Zhang J, Cheng H, Zhang J, Ni X, Wang C, Xu C, Geng H, et al: Novel variants in Dnah9 lead to nonsyndromic severe asthenozoospermia. Reprod Biol Endocrinol. 19:272021. View Article : Google Scholar : PubMed/NCBI

10 

Fassad MR, Shoemark A, Legendre M, Hirst RA, Koll F, le Borgne P, Louis B, Daudvohra F, Patel MP, Thomas L, et al: Mutations in outer dynein arm heavy chain DNAH9 cause motile cilia defects and situs inversus. Am J Hum Genet. 103:984–994. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Chen W, Zhang Y, Shen L, Zhu J, Cai K, Lu Z, Zeng W, Zhao J and Zhou X: Biallelic DNAH9 mutations are identified in Chinese patients with defective left-right patterning and cilia-related complex congenital heart disease. Hum Genet. 141:1339–1353. 2022. View Article : Google Scholar : PubMed/NCBI

12 

Loges NT, Antony D, Maver A, Deardorff MA, Güleç EY, Gezdirici A, Nöthe-Menchen T, Höben IM, Jelten L, Frank D, et al: Recessive DNAH9 loss-of-function mutations cause laterality defects and subtle respiratory ciliary-beating defects. Am J Hum Genet. 103:995–1008. 2018. View Article : Google Scholar : PubMed/NCBI

13 

Zhang T, Yuan H, Zhu H, Ying Y, Ding J, Ding H, Shi X, He Y, Pan H and Zhong Y: Fetal congenital heart disease caused by compound heterozygous mutations in the DNAH9 gene: A case report. Front Genet. 12:7717562021. View Article : Google Scholar : PubMed/NCBI

14 

Feng J, Li J, Du Y, Shi T, Sharma L and Jie Z: Case report: Rare dynein axonemal heavy chain 9 mutations in a han-Chinese patient with kartagener syndrome. Front Med (Lausanne). 9:8939682022. View Article : Google Scholar : PubMed/NCBI

15 

Takeuchi K, Xu Y, Ogawa S, Ikejiri M, Nakatani K, Gotoh S, Usui S, Masuda S, Nagao M and Fujisawa T: A pediatric case of productive cough caused by novel variants in DNAH9. Hum Genome Var. 8:32021. View Article : Google Scholar : PubMed/NCBI

16 

Isa HM, Alkharsi FA, Busehail MY and Haider F: A Novel DNAH9 gene mutation causing primary ciliary dyskinesia with an unusual association of jejunal atresia in a bahraini child. Cureus. 14:e329642022.PubMed/NCBI

17 

Tate G: Whole-exome sequencing reveals a combination of extremely rare single-nucleotide polymorphism of DNAH9 and RSPH1 genes in a Japanese fetus with situs viscerum inversus. Med Mol Morphol. 54:275–280. 2021. View Article : Google Scholar : PubMed/NCBI

18 

Chen Y, Chen Y, Shi C, Huang Z, Zhang Y, Li S, Li Y, Ye J, Yu C, Li Z, et al: SOAPnuke: A MapReduce acceleration-supported software for integrated quality control and preprocessing of high-throughput sequencing data. Gigascience. 7:1–6. 2018. View Article : Google Scholar

19 

Li H and Durbin R: Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 25:1754–1760. 2009. View Article : Google Scholar : PubMed/NCBI

20 

He WB, Tu CF, Liu Q, Meng LL, Yuan SM, Luo AX, He FS, Shen J, Li W, Du J, et al: DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing. J Med Genet. 55:198–204. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Qi H, Pan D, Zhang Y, Zhu Y, Zhang X and Fu T: NEXMIF combined with KIDINS220 gene mutation caused neurodevelopmental disorder and epilepsy: One case report. Actas Esp Psiquiatr. 52:588–594. 2024. View Article : Google Scholar : PubMed/NCBI

22 

Li G, Chen Y, Han X, Li N and Li S: Concurrent of compound heterozygous variant of a novel in-frame deletion and the common hypomorphic haplotype in TBX6 and inherited 17q12 microdeletion in a fetus. BMC Pregnancy Childbirth. 24:4562024. View Article : Google Scholar : PubMed/NCBI

23 

McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M and DePristo MA: The genome analysis toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20:1297–1303. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 17:405–424. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Hamada H, Meno C, Watanabe D and Saijoh Y: Establishment of vertebrate left-right asymmetry. Nat Rev Genet. 3:103–113. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Komatsu Y and Mishina Y: Establishment of left-right asymmetry in vertebrate development: The node in mouse embryos. Cell Mol Life Sci. 70:4659–4666. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Nonaka S, Shiratori H, Saijoh Y and Hamada H: Determination of left-right patterning of the mouse embryo by artificial nodal flow. Nature. 418:96–99. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Essner JJ, Vogan KJ, Wagner MK, Tabin CJ, Yost HJ and Brueckner M: Conserved function for embryonic nodal cilia. Nature. 418:37–38. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Djenoune L, Mahamdeh M, Truong TV, Nguyen CT, Fraser SE, Brueckner M, Howard J and Yuan S: Cilia function as calcium-mediated mechanosensors that instruct left-right asymmetry. Science. 379:71–78. 2023. View Article : Google Scholar : PubMed/NCBI

30 

Katoh TA, Omori T, Mizuno K, Sai X, Minegishi K, Ikawa Y, Nishimura H, Itabashi T, Kajikawa E, Hiver S, et al: Immotile cilia mechanically sense the direction of fluid flow for left-right determination. Science. 379:66–71. 2023. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu X, Zhou JL, Yang C, Zhou H, He W and Yang J: Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease. Mol Med Rep 32: 198, 2025.
APA
Liu, X., Zhou, J., Yang, C., Zhou, H., He, W., & Yang, J. (2025). Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease. Molecular Medicine Reports, 32, 198. https://doi.org/10.3892/mmr.2025.13563
MLA
Liu, X., Zhou, J., Yang, C., Zhou, H., He, W., Yang, J."Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease". Molecular Medicine Reports 32.1 (2025): 198.
Chicago
Liu, X., Zhou, J., Yang, C., Zhou, H., He, W., Yang, J."Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease". Molecular Medicine Reports 32, no. 1 (2025): 198. https://doi.org/10.3892/mmr.2025.13563
Copy and paste a formatted citation
x
Spandidos Publications style
Liu X, Zhou JL, Yang C, Zhou H, He W and Yang J: Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease. Mol Med Rep 32: 198, 2025.
APA
Liu, X., Zhou, J., Yang, C., Zhou, H., He, W., & Yang, J. (2025). Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease. Molecular Medicine Reports, 32, 198. https://doi.org/10.3892/mmr.2025.13563
MLA
Liu, X., Zhou, J., Yang, C., Zhou, H., He, W., Yang, J."Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease". Molecular Medicine Reports 32.1 (2025): 198.
Chicago
Liu, X., Zhou, J., Yang, C., Zhou, H., He, W., Yang, J."Novel compound heterozygous mutation in <em>DNAH9</em> causes complex congenital heart disease". Molecular Medicine Reports 32, no. 1 (2025): 198. https://doi.org/10.3892/mmr.2025.13563
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