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CEP104 gene may involve in the pathogenesis of a new developmental disorder other than joubert syndrome

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Abstract

Background

The CEP104 gene (OMIM: 616,690) encodes the centrosome protein 104 (CEP104) that is involved in cilia function. Pathogenic variants in this gene have been described in four patients diagnosed with Joubert syndrome (JBTS) 25. Here, we challenged the concept that pathogenic variants in CEP104 gene are only involved in the development of JBTS 25.

Methods and results

In a clinical setting, whole-exome sequencing (WES) was applied to investigate pathogenic variants in patients with unexplained developmental delay or intellectual disability (DD/ID).WES revealed a novel homozygous nonsense variant (c.643C > T) in CEP104 (NM _014704.3) in a girl with mild intellectual disability, hypotonia, and imbalanced gait. Her brain MRI data did not show molar tooth sign (MTS) or any other brain anomalies.

Conclusion

Our study introduced a novel variant in the CEP104 gene that results in an ID phenotype other than JBTS25. Comparison of her phenotype with that of eight previously published DD/ID patients harboring pathogenic variants in CEP104 gene revealed that more than half of them did not show JBTS related symptoms. Therefore, we suggest that the CEP104 gene might also be involved in a disorder other than JBTS 25, a point that deserves to be emerged in the OMIM database.

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Abbreviations

BUN:

Blood urea nitrogen

CBC:

Complete blood count

CC:

Coiled coil

CPK:

Creatine phosphate kinase

DD:

Developmental delay

EEG:

Electroencephalography

EMG:

Electromyography

ID:

Intellectual disability

JBTS:

Joubert syndrome

MRI:

Magnetic resonance imaging

MTS:

Molar tooth sign

NCV:

Nerve conduction velocity

OMA:

Ocular motor apraxia

OMIM:

Online Mendelian inheritance in man

TFT:

Thyroid function tests

TOG:

Tumor-overexpressed gene

WES:

Whole-exome sequencing

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Acknowledgements

We appreciate Tehran University of Medical Sciences for supporting this study under the grant ID of 1400-3-101-55097. We also appreciate the parents of the proband for participation in this project.

Funding

This work was supported by Tehran University of Medical Sciences (Grant number [1400–3-101–55097]).

Author information

Authors and Affiliations

  1. Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Reza Shervin Badv & Maryam Rasoulinezhad

  2. Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mojdeh Mahdiannasser

  3. Ronash Medical Genetics Center, Tehran, Iran

    Laleh Habibi

  4. Maternal, Fetal and Neonatal Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Ali Rashidi-Nezhad

  5. Genetic Ward, Yas Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

    Ali Rashidi-Nezhad

  6. Maternal, Fetal and Neonatal Research Center, Family Health Research Institute, Valiasr Hospital, 2nd floor, Baqerkhan st., P.O.Box:1419733141, Tehran, Iran

    Ali Rashidi-Nezhad

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  1. Reza Shervin Badv
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Contributions

ARN, RS and MM contributed to the study conception and design. Clinical evaluation and data collection were performed by RS and MR, Data analysis was performed by ARN and LH. The first draft of the manuscript was written by MM and MR. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ali Rashidi-Nezhad.

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Conflict of interest

The authors declare no competing interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tehran University of Medical Sciences (Date August 1, 2021/No:55097).

Informed consent

Written informed consent was obtained from the parents.

Consent for publication

The authors affirm that human research participants provided informed consent for publication of patient WES data and clinicopathological features.

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Badv, R.S., Mahdiannasser, M., Rasoulinezhad, M. et al. CEP104 gene may involve in the pathogenesis of a new developmental disorder other than joubert syndrome. Mol Biol Rep 49, 7231–7237 (2022). https://doi.org/10.1007/s11033-022-07353-w

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  • DOI: https://doi.org/10.1007/s11033-022-07353-w

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