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Mutational analysis of CYP1B1 gene in Iranian pedigrees with glaucoma reveals known and novel mutations

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Abstract

Purpose

Primary congenital glaucoma (PCG) (OMIM#231,300) can be caused by pathogenic sequence variations in CYP1B1, LTBP2, MYOC and PXDN genes. The purpose of this study was to investigate mutations in the CYP1B1 gene in families affected with primary congenital glaucoma (PCG) using linkage analysis and Sanger sequencing.

Methods

A total number of four families with nine affected PCG patients during six months were included in this study. The mutations were identified by homozygosity mapping to find the linked loci and then direct sequencing of all coding exons, the exon–intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA obtained from affected family members and their parents. Moreover, bioinformatic tools were applied to study mutation effect on protein structure and function.

Results

A total of four mutations were identified, and three of these were novel. Two were missense mutations: One was truncating mutation, and the other was an in-frame deletion. Mutations in CYP1B1 could fully explain the PCG phenotype in all of the patients. Also, the bioinformatic study of the mutations showed the structure of the protein is affected, and it is well conserved among similar species.

Conclusion

In this study, we identified 4 CYP1B1 mutations, 3 of which were novel. In silico analysis of identified mutations confirmed their molecular pathogenicity. A similar analysis will help understand the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG.

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Data availability

The data that support the findings of this study are available.

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Acknowledgements

This study has been granted by the Tabriz University of Medical Sciences (Grant number: 63772). We would like to thank the Semnan University of Medical Sciences for their collaboration and support. Moreover, we would like to express our sincere thanks to the family members who took part in this study and profoundly appreciate their cooperation which made this study possible

Funding

This study has been granted by the Tabriz University of Medical Sciences (Grant number: 63772).

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Babak Emamalizadeh, Yousef Daneshmandpour, Somayeh Kazeminasb & Zahra Bahmanpour

  2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Yousef Daneshmandpour & Zahra Bahmanpour

  3. Department of Pediatrics, School of Medicine, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Ehsan Aghaei Moghadam

  4. Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Elham Alehabib & Somayeh Alinaghi

  5. Department of Medical Genetics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Hossein Darvish

  6. Department of Ophthalmology, Torfeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Azadeh Doozandeh

  7. Department of Biology, Faculty of Basic Sciences, East Tehran Branch (Ghiamdasht), Islamic Azad University, Tehran, Iran

    Minoo Atakhorrami

  8. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Hossein Darvish

Authors
  1. Babak Emamalizadeh
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  2. Yousef Daneshmandpour
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  3. Somayeh Kazeminasb
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  7. Somayeh Alinaghi
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  9. Minoo Atakhorrami
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  10. Hossein Darvish
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Contributions

Babak Emamalizadeh and Hossein Darvish took part in conceptualization; Babak Emamalizadeh, Yousef Daneshmandpour and Somayeh Kazeminasb were involved in methodology; Yousef Daneshmandpour, Zahra Bahmanpour, Somayeh Alinaghi and Azadeh Doozandeh carried out formal analysis and investigation; Ehsan Aghaei Moghadam and Elham Alehabib wrote the original draft; Hossein Darvish, Ehsan Aghaei Moghadam, Zahra Bahmanpour and Azadeh Doozandeh wrote, reviewed and edited the manuscript; Hossein Darvish and Babak Emamalizadeh acquired the funding; Minoo Atakhorrami and Hossein Darvish had contributed to supervision.

Corresponding authors

Correspondence to Minoo Atakhorrami or Hossein Darvish.

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Conflict of interest

There are no financial or other conflicts of interest.

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The participation consent has been received from all participants.

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The publication consent has been received from all participants.

Ethical approval

The study has been approved by ethics committee of Tabriz University of medical Sciences (Code: IR.TBZMED.REC.1398.643)

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Emamalizadeh, B., Daneshmandpour, Y., Kazeminasb, S. et al. Mutational analysis of CYP1B1 gene in Iranian pedigrees with glaucoma reveals known and novel mutations. Int Ophthalmol 41, 3269–3276 (2021). https://doi.org/10.1007/s10792-021-01888-w

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  • DOI: https://doi.org/10.1007/s10792-021-01888-w

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