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Novel Gene Variants Associated with Primary Ciliary Dyskinesia

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Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objectives

To determine the demographic, clinical, and genetic profile of Turkish Caucasian PCD cases.

Methods

Targeted next-generation sequencing (t-NGS) of 46 nuclear genes was performed in 21 unrelated PCD cases. Sanger sequencing confirmed of potentially disease-related variations, and genotype–phenotype correlations were evaluated.

Results

Disease-related variations were identified in eight different genes (CCDC39, CCDC40, CCDC151, DNAAF2, DNAAF4, DNAH11, HYDIN, RSPH4A) in 52.4% (11/21) of the cases. The frequency of variations for CCDC151, DNAH11, and DNAAF2 genes which were highly mutated genes in the cohort was 18% in 11 patients. Each of the remaining gene variations was detected once (9%) in different patients. The variants, p.R482fs*12 in CCDC151, p.E216* in DNAAF2, p.I317* in DNAAF4, p.L318P and p.R1865* in DNAH11, and p.N1505D and p.L1167P in HYDIN gene were identified as novel variations. Interestingly, varying phenotypic findings were identified even in patients with the same mutation, which once again confirmed that PCD has a high phenotypic heterogeneity and shows individual differences.

Conclusion

This t-NGS panel is potentially helpful for exact and rapid identification of reported/novel PCD-disease–causing variants to establish the molecular diagnosis of ciliary diseases.

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Data Availability

On request.

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Acknowledgements

The authors would like to thank all families for their valuable participation; Burcu Coban Taner, Cihan Erdinc Gulsev, and Nazli Kocaefe for their kind technical assistance, and Martha Knight and Lynn P. Chorich for language editing.

Funding

This research was supported by Akdeniz University Scientific Research Projects Council (TSA-2018–3522) and TUBITAK 2209/A (project#1919B01100081), Turkey.

Author information

Authors and Affiliations

  1. Department of Medical Biology and Genetics, School of Medicine, Akdeniz University, Antalya, 07070, Turkey

    Durkadin Demir Eksi, Elanur Yilmaz, Gizem Erduran & Ozgul M. Alper

  2. Department of Medical Biology, School of Medicine, Alanya Alaaddin Keykubat University, Antalya, 07425, Turkey

    Durkadin Demir Eksi

  3. Department of Medical Genetics & Koç University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koç University, Istanbul, Turkey

    Elanur Yilmaz

  4. Department of Pediatric Pulmonology, School of Medicine, Akdeniz University, Antalya, Turkey

    A. Erdem Basaran & Aysen Bingol

  5. Department of Pediatric Genetics, School of Medicine, Akdeniz University, Antalya, Turkey

    Banu Nur & Ercan Mihci

  6. Department of Pediatric Pulmonology, School of Medicine, Marmara University, Istanbul, Turkey

    Bulent Karadag

Authors
  1. Durkadin Demir Eksi
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  2. Elanur Yilmaz
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  3. A. Erdem Basaran
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  4. Gizem Erduran
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  5. Banu Nur
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  6. Ercan Mihci
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  7. Bulent Karadag
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  8. Aysen Bingol
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  9. Ozgul M. Alper
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Contributions

DDE, EY, and OMA designed the study; DDE, EY, GE performed molecular genetic studies; AEB, BN, EM, and AB did patient evaluation; EY, DDE, GE, and OMA performed data analyses; EY, DDE, and OMA wrote the paper. OMA will act as the guarantor for this paper.

Corresponding authors

Correspondence to Durkadin Demir Eksi or Ozgul M. Alper.

Ethics declarations

Ethics Approval

All procedures carried out in the study comply with the ethical standards of the institutional and/or national research ethics committee [protocol number 70904504/58 dated Feb 02, 2015] and the 1964 Helsinki Declaration and its subsequent changes or comparable standards of ethics.

Consent to Participate

Informed consent was obtained from all individuals included in this study.

Conflict of Interest

None.

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Durkadin Demir Eksi and Elanur Yilmaz are joint first authors

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Demir Eksi, D., Yilmaz, E., Basaran, A.E. et al. Novel Gene Variants Associated with Primary Ciliary Dyskinesia. Indian J Pediatr 89, 682–691 (2022). https://doi.org/10.1007/s12098-022-04098-z

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  • DOI: https://doi.org/10.1007/s12098-022-04098-z

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