Whole exome sequencing identifies a novel NRL mutation in a Chinese family with autosomal dominant retinitis pigmentosa

Gao, M., Zhang, S., Liu, C., Qin, Y., Archacki, S., Jin, L., Wang, Y., Liu, F., Chen, J., Liu, Y., Wang, J., Huang, M., Liao, S., Tang, Z., Guo, A.Y., Jiang, F., Liu, M.
Molecular Vision   22: 234-42 (Journal)
Registered Authors
Chen, Jiaxiang, Liao, Shengjie, Liu, Fei, Liu, Ying, Qin, Yayun, Wang, Jiuxiang
MeSH Terms
  • Adult
  • Aged
  • Asian People/genetics*
  • Basic-Leucine Zipper Transcription Factors/genetics*
  • China/epidemiology
  • Electroretinography
  • Exome/genetics*
  • Eye Proteins/genetics*
  • Female
  • Fluorescein Angiography
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Point Mutation*
  • Polymerase Chain Reaction
  • Retinitis Pigmentosa/diagnosis
  • Retinitis Pigmentosa/genetics*
  • Sequence Analysis, DNA
  • Tomography, Optical Coherence
  • Visual Field Tests
  • Visual Fields
  • Young Adult
To investigate the genetic basis and its relationship to the clinical manifestations in a four generation Chinese family with autosomal dominant retinitis pigmentosa.
Ophthalmologic examinations including fundus photography, fundus autofluorescence imaging, fundus fluorescein angiography, optical coherence tomography, and a best-corrected visual acuity test were performed to define the clinical features of the patients. We extracted the genomic DNA from peripheral blood samples. The proband's genomic DNA was submitted to the whole exome sequencing.
Whole exome sequencing and the subsequent data analysis detected six candidate mutations in the proband of this pedigree. The novel c.146 C>T mutation in NRL was found to be the only mutation that co-segregated with the disease in this pedigree. This mutation resulted in a substitution of proline by a leucine at position 49 of NRL protein (p.P49L). Most importantly, the proline residue at position 49 of NRL is highly conserved from zebrafish to humans. The c.146 C>T mutation was not observed in 200 control individuals. What's more, we performed the luciferase activity assay to prove that this mutation we detected alters the NRL protein function.
The c.146 C>T mutation in NRL gene causes autosomal dominant retinitis pigmentosa for this family. Our finding not only expands the mutation spectrum of NRL, but also demonstrates that whole-exome sequencing is a powerful strategy to detect causative genes and mutations in RP patients. This technique may provide a precise diagnosis for rare heterogeneous monogenic disorders such as RP.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes