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A novel mutation in RDH5 gene causes retinitis pigmentosa in consanguineous Pakistani family

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Abstract

Retinitis pigmentosa (RP) is the most frequent genetically and clinically heterogeneous inherited retinal degeneration. To date, more than 80 genes have been identified that cause autosomal dominant, autosomal recessive and X linked RP. However, locus and allelic heterogeneity of RP has not been fully captured yet. This heterogeneity and lack of an accurate genotype phenotype correlation makes molecular dissection of the disease more difficult. The present study was designed to characterize the underlying pathogenic variants of RP in Pakistan. For this purpose, a large consanguineous family with RP phenotype showing autosomal recessive mode of inheritance was selected after a complete ophthalmological examination. Next generation sequencing was used for the identification of molecular determinant followed by Sanger-sequencing for confirmation. After sequence analysis a novel homozygous missense mutation, (c.602 C > T) in exon 4 of the RDH5 gene (MIM: 601617) was identified. This mutation resulted in substitution of phenyl alanine for serine at amino acid 201 (p.Ser201Phe) of the RDH5 gene. The same mutation was not detected in the 200 ethnically-matched control samples by Sanger sequencing. The identified mutant allele segregated in homozygous fashion in all the affected individuals of pedigree. Identification of this mutation reveals the allelic heterogeneity of RDH5 in patients with RP phenotype. The findings of this study demonstrate the clinical significance of next generation sequencing to understand the molecular basis of diseases and would help to reveal new proteins and their function in visual cycle will pave the way for early diagnosis, genetic counseling and better therapeutic inventions.

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Acknowledgements

The authors gratefully acknowledge the Higher Education Commission (HEC) Pakistan for providing the funds, Human Molecular Genetics Lab NIBGE for continual generous support during this research work and Professor Dr Hanno Bolz Cologne Centre for Genomics (CCG), University of Cologne, Germany, for sequencing. Dr. Muhammad Sajid Hussain University of Cologne, Germany, helped in the interpretation of sequencing data.

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Authors and Affiliations

  1. Department of Biochemistry, Govt. College University, Faisalabad, Pakistan

    Neelam Sultan, Shazia Anwer Bukhari & Muhammad Qasim

  2. Akhuwat Faisalabad Institute of Research Science and Technology, Faisalabad, Pakistan

    Irfan Ali

  3. Centre of Agricultural Biochemistry and Biotechnology, University of Agriculture, Faisalabad, Pakistan

    Irfan Ali

  4. National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan

    Shahid Mahmood Baig

  5. Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Pakistan

    Muhammad Asif

  6. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia

    Muhammad Imran Naseer & Mahmood Rasool

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  1. Neelam Sultan
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  2. Irfan Ali
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  3. Shazia Anwer Bukhari
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Correspondence to Muhammad Asif.

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Neelam Sultan, Irfan Ali, Shazia Anwer Bukhari, Shahid Mahmood Baig, Muhammad Asif, Muhammad Qasim, Muhammad Imran Naseer, Mahmood Rasool, declare that they have no conflict of interest.

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Sultan, N., Ali, I., Bukhari, S.A. et al. A novel mutation in RDH5 gene causes retinitis pigmentosa in consanguineous Pakistani family. Genes Genom 40, 553–559 (2018). https://doi.org/10.1007/s13258-018-0657-5

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  • DOI: https://doi.org/10.1007/s13258-018-0657-5

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