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A novel mutation in the PRPF31 in a North Indian adRP family with incomplete penetrance

Documenta Ophthalmologica volume 137, pages 103–119 (2018)Cite this article

Abstract

Purpose

To identify the underlying genetic defect for non-syndromic autosomal dominant retinitis pigmentosa (adRP) with incomplete penetrance in a North Indian family.

Methods

Family history and clinical data were collected. Linkage analysis using 72 fluorescently labeled microsatellite markers flanking all the 26 candidate genes known for adRP was performed. Mutation screening in candidate gene at the mapped region was performed by bi-directional DNA sequencing.

Results

Positive two-point lod scores > 1.0 (θ = 0.000) suggestive of linkage were obtained with markers D19S572, D19S927 and D19S926 at 19q13.42, in the vicinity of PRPF31 gene. Mutation screening in all the 14 exonic regions and intron–exon boundaries of PRPF31 revealed a novel change, i.e. c.896G>A (p.Cys299Tyr) in exon eight. The observed change segregated in heterozygous form in all the six affected members and in three carriers, consistent with incomplete penetrance. This substitution was not observed in tested 15 unaffected members and in 200 ethnically matched controls.

Conclusion

Present study describes mapping of a locus for non-syndromic adRP with incomplete penetrance at 19q13.42 in a North Indian family and identifies a novel missense mutation (p.Cys299Tyr) in PRPF31 localized at the mapped interval. The observed substitution lies in the NOP domain of PRPF31 that exhibit RNA and protein binding surfaces and thus may interfere in the formation of spliceosome complex. Due to p.Cys299Tyr substitution hydrogen bonds are generated, which may result in conformational changes and PRPF31 protein deformity. Present findings further substantiate the role of PRPF31 in adRP with incomplete penetrance and expand the mutation spectrum of PRPF31.

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Acknowledgements

The authors are grateful to all the family members for their participation in this study and for their kind cooperation. We are thankful to the retina experts at the Dr. Daljit Singh Eye Hospital, Amritsar, Punjab and Dr. Shroff’s Charity Eye Hospital, New Delhi, India, for undertaking ophthalmic examinations of all the members of this family.

Funding

This work was supported in part by grant sanctioned from Department of Biotechnology, India BT/IN/German/13/VK/2010 IND 10/036 to VV under the framework of Indo-German bilateral cooperation for research. Authors are also thankful to DST-PURSE scheme from DST, Government of India for providing research grant to GNDU.

Author information

Author notes

  1. Sofia Bhatia and Shiwali Goyal have contributed equally to this work.

Affiliations

  1. Department of Human Genetics, Guru Nanak Dev University (GNDU), Amritsar, Punjab, 143005, India

    Sofia Bhatia, Shiwali Goyal & Vanita Vanita

  2. Dr. Daljit Singh Eye Hospital, Amritsar, Punjab, India

    Indu R. Singh & Daljit Singh

Authors
  1. Sofia Bhatia
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  2. Shiwali Goyal
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  3. Indu R. Singh
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  4. Daljit Singh
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  5. Vanita Vanita
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Corresponding author

Correspondence to Vanita Vanita.

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The authors declare that they have no conflict of interest.

Human and animal rights

The study conforms to the Declaration of Helsinki. No animals were used.

Informed consent

The present study adhered to the Tenets of the Declaration of Helsinki and was approved by the ethics committee of Guru Nanak Dev University, Amritsar. Written informed consent was obtained from all the participating individuals.

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Bhatia, S., Goyal, S., Singh, I.R. et al. A novel mutation in the PRPF31 in a North Indian adRP family with incomplete penetrance. Doc Ophthalmol 137, 103–119 (2018). https://doi.org/10.1007/s10633-018-9654-x

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  • DOI: https://doi.org/10.1007/s10633-018-9654-x

Keywords

  • Autosomal dominant retinitis pigmentosa
  • PRPF31
  • Linkage analysis
  • Mutation screening
  • RP11 locus
  • Two-point lod scores