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The molecular landscape of oculocutaneous albinism in India and its therapeutic implications

European Journal of Human Genetics (2023)Cite this article

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Abstract

Oculocutaneous albinism is an inherited disorder of melanin biosynthesis, characterized by absent or reduced pigmentation of the skin, hair, and eyes. Molecular alterations of genes that cause non-syndromic albinism in Asian Indians are poorly characterized. This information would be useful for developing therapies for this disorder. We analyzed 164 persons with non-syndromic albinism, belonging to unrelated families from all parts of India, for molecular changes in the causative genes. Subjects with white hair, white skin, and red iris had their tyrosinase gene sequenced and were also tested by MLPA for deletions/duplications. Subjects with negative results or with darker skin, golden/brown or darker hair had sequencing of TYR, P, TYRP1, SLC45A2 and GPR143 genes. Pathogenic variants in TYR (OCA1) were observed in 139 (84.7%) patients, in the P gene (OCA2) in 20 (12.2%), in TYRP1 (OCA3) in two (1.2%), in SLC45A2 (OCA 4) in one (0.61%), and in GPR143 (X-linked ocular albinism) in two (1.2%) patients. Of 278 alleles with variants in TYR, 179 (64.3%) alleles had (p.R278*) alteration, suggesting the possibility of therapy with a stop codon readthrough molecule. We report 20 patients with 13 disease associated variants in the P gene and 18 novel pathogenic variants in TYR, P, TYRP1, SLC45A2 and GPR143 genes. The data are compared with those reported from India, Pakistan and rest of the world. The therapeutic options in albinism are briefly described, opening this field for future therapies.

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Data availability

Data may be requested from the authors and will be made available subject to patient consent. The variants are submitted to LOVD V3.0 as individual # 00435430, 00435573, 00435574, 00435575, 00436615, 00436616, 00436617, 00436618, 00436619, 00436620, 00436621, 00436622, 00436624, 00436625,00436626,00436627,00436636,00436637,00436638,00436639,00436640,00436641,00436642,00436643,00466644,00436645,00436666,00436667,00436668,00436669,00436670,00436671,00436675,00436676,00436777,00436778,00436784,00436785,00436786,00436787,00436788.

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Acknowledgements

Sincere thanks to the children, families and clinicians who took part in this project. Thanks to Molecular Genetics Staff for technical help. Thanks also to Medgenome for NGS sequencing of some of the samples.

Funding

This work was supported by Sir Ganga Ram Hospital. No external funding was used.

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Author notes

  1. These authors contributed equally: Sudha Kohli, Ishwar Verma.

Authors and Affiliations

  1. Institute of Medical Genetics and Genomics, Ganga Ram Institute of Postgraduate Medical Education and Research, Sir Ganga Ram Hospital, New Delhi, 110060, India

    Sudha Kohli, Renu Saxena, Ratna Dua Puri, Sunita Bijarnia Mahay, Swasti Pal, Sudhisha Dubey, Veronica Arora & Ishwar Verma

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Contributions

SK: Data generation and analysis of Sanger and Next generation sequencing of panel of OCA genes, analyzed and interpreted data, writing and revising manuscript. RS: Data generation and analysis of Sanger and Next generation sequencing of panel of OCA genes, analyzed data, revised manuscript. RP: Enrolling patients, Gathering data, collating the mutations, Writing and revising manuscript. SB: Enrolling patients, Gathering data, Writing and revising manuscript. SP: Whole exome data collection, checking and formatting references, revising manuscript. SD: Analysis of Next generation sequencing of panel of OCA genes, revising manuscript. VA: Enrolling patients, collating mutations, revising manuscript. IV: Enrolling patients, analyzed and interpreted data, planned and executed project, wrote and critically reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sudha Kohli or Ishwar Verma.

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Ethics approval was obtained from the Institutional Ethics Review Board of Sir Ganga Ram Hospital vis ethical clearance letter no, EC/07/23/2311.

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Kohli, S., Saxena, R., Puri, R.D. et al. The molecular landscape of oculocutaneous albinism in India and its therapeutic implications. Eur J Hum Genet (2023). https://doi.org/10.1038/s41431-023-01496-5

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  • DOI: https://doi.org/10.1038/s41431-023-01496-5

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