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Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing

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Abstract

Purpose

The present study aimed to identify the molecular etiology of non-syndromic congenital cataract (CC) using whole-exome sequencing (WES) analysis.

Methods

In the present study, ophthalmologic results and pedigree analysis of the families of 12 patients with non-syndromic CC were evaluated. WES analysis was conducted after DNA was isolated from peripheral blood samples obtained from the patients.

Results

Twelve non-syndromic probands (10 males and 2 females) with bilateral CC were included in the study. Patient age ranged between 1 and 11 months. WES analysis showed pathogenic/likely pathogenic variant in 7 (58%) of the 12 families and variant of unknown significance (VUS) in 5 (42%) of them. All the 13 different variants detected in 9 different CC-related genes were co-segregated with the disease. Autosomal dominant inheritance was found in 7 (58%) of the families and autosomal recessive inheritance was found in 5 (42%) of them.

Conclusion

To the best of our knowledge, the present research is one of the limited numbers of studies in the Turkish population in which genetically heterogeneous non-syndromic CC was investigated using WES analysis. Novel variants that we identified in DNMBP, LSS, and WFS1 genes, which are rarely associated with the CC phenotype, have contributed to the mutation spectrum of this disease. Identifying the relevant molecular genetic etiology allows accurate genetic counseling to be provided to the families.

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Data availability

The authors declare that materials described in the manuscript, including all relevant raw data, will be freely available to any scientist wishing to use them for noncommercial purposes, without breaching participant confidentiality. Moreover, the authors ensure that their datasets are presented in the main manuscript.

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Funding

The authors did not receive support from any organization for the submitted work.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University, Ortahisar, Trabzon, Turkey

    Ayberk Türkyılmaz

  2. Department of Ophthalmology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey

    Ayşin Tuba Kaplan, Sibel Öskan Yalçın & Şaban Şimşek

  3. Department of Pediatric Neurology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey

    Safiye Güneş Sağer

Authors
  1. Ayberk Türkyılmaz
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  2. Ayşin Tuba Kaplan
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  3. Sibel Öskan Yalçın
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  4. Safiye Güneş Sağer
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  5. Şaban Şimşek
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by AT, ATK, SÖY, SGS, SS. Genetic analysis was performed by AT. The first draft of the manuscript was written by AT and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ayberk Türkyılmaz.

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Conflict of ınterest

All the authors declare that they have no conflict of interest and no financial disclosure.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey (decision date: 28 April 2021, No. 2021/514/200/3).

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Türkyılmaz, A., Kaplan, A.T., Öskan Yalçın, S. et al. Identification of novel variants in Turkish families with non-syndromic congenital cataracts using whole-exome sequencing. Int Ophthalmol 43, 4573–4583 (2023). https://doi.org/10.1007/s10792-023-02857-1

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  • DOI: https://doi.org/10.1007/s10792-023-02857-1

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