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Impact of RB1 gene screening from blood collected on a single day from 411 family members of 113 Retinoblastoma survivors in India

Eye (2024)Cite this article

Subjects

Abstract

Objectives

To analyse the profile and implication of genetic testing in a cohort of retinoblastoma (RB) patients and their families conducted on a single day during World Retinoblastoma Awareness Week 2017.

Methods

Retrospective analysis of blood samples were collected from 411 subjects, including 113 probands at a camp organised for RB awareness and were analysed for RB1 mutations by Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). If germline mutations were detected, the parents and siblings of the proband were tested for the same mutation.

Results

Germline RB1 mutations were identified in 61/113(54%) probands with a mutation detection rate of 96% (47/49) and 22% (14/64) for bilateral and unilateral RB, respectively. Ten novel pathogenic mutations were identified. Splice mutation was most common (31%) followed by nonsense mutation (26%). The mean age at RB diagnosis was significantly lower in patients having germline RB1 mutation (mean 10.7 months ±2.5) compared to those without (mean 27.2 months ±6.5) (p = <0.0001). Parental transmission of the mutant allele was detected in 15/61(25%) cases of which 11(18%) parents were unaffected indicating incomplete penetrance. The origin of the variant allele was both paternal (n = 7) and maternal (n = 4) wherein 5 were bilateral and 6 unilateral.

Conclusions

The detection of a germline mutation impacts the proband and family members due to its implications on change in prognosis, frequency of subsequent evaluations, screening for ocular and non-ocular cancers, and surveillance of family and future progeny.

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Fig. 1: Distribution and schematic representation of mutations across RB1 gene.
Fig. 2: Representative pedigree of families with low penetrance RB1 mutation.
Fig. 3: Post testing surveillance in familial RB.

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Data availability

The data supporting this study’s findings are available from the corresponding author upon request.

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Acknowledgements

We thank all our patients who participated in our study. We would also like to thank Sun Foundation and our colleagues in the department of vitreoretinal and molecular genetics for providing their support.

Presentations Part of this study was presented at the International Society of Genetic Eye Diseases and Retinoblastoma, Giessen, Germany, August 29–31, 2019.

Funding

No funding was received for this study.

Author information

Authors and Affiliations

  1. Department of Molecular Genetics, Aravind Medical Research Foundation, Madurai, India

    Ayyasamy Vanniarajan & Karuvel Kannan Saraswathi

  2. Department of Molecular Biology, Aravind Medical Research Foundation, Affiliated to Alagappa University, Karaikudi, India

    Ayyasamy Vanniarajan & Karuvel Kannan Saraswathi

  3. Department of Vitreoretina Services, Aravind Eye Hospital, Chennai, India

    Puja Maitra

  4. Department of Pediatric Retina and Ocular Oncology, Aravind Eye Hospital, Coimbatore, India

    Parag K. Shah

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  1. Ayyasamy Vanniarajan
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  4. Parag K. Shah
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Contributions

Conceptualisation- PKS and AV, data curation-PKS, PM and AV, data analysis- PM, KKS and AV, paper writing- PM, KKS, PKS and AV. All authors accepted the final draft of the paper.

Corresponding author

Correspondence to Parag K. Shah.

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Competing interests

The authors declare no competing interests.

Ethics statement

This study was approved by the Institutional Human Ethics Committee, PSG IMS&R (Project number 17/109).

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Vanniarajan, A., Maitra, P., Saraswathi, K.K. et al. Impact of RB1 gene screening from blood collected on a single day from 411 family members of 113 Retinoblastoma survivors in India. Eye (2024). https://doi.org/10.1038/s41433-024-02955-z

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  • DOI: https://doi.org/10.1038/s41433-024-02955-z

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