title: Whole exome sequencing identifies a novel NRL mutation in a Chinese family with autosomal dominant retinitis pigmentosa.
abstract: OBJECTIVE
  To investigate the genetic basis and its relationship to the clinical manifestations in a four generation Chinese family with autosomal dominant retinitis pigmentosa.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: Nursing School of HuBei Polytechnic Institute; Xiaogan Central Hospital, Xiaogan, Hubei, PR China.
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Center for cardiovascular Genetics, Department of Molecular Cardiology and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Stephen
authors.initials: S
authors.lastname: Archacki
authors.affiliation: Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jin
authors.affiliation: The First People's Hospital of Tianmen, Hubei, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Jiuxiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Mi
authors.initials: M
authors.lastname: Huang
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Liao
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Biomedical Engineering, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: An Yuan
authors.initials: AY
authors.lastname: Guo
authors.affiliation: Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Fagang
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D002681:China / Q000453:epidemiology; D004596:Electroretinography; D059472:Exome / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests; D014794:Visual Fields; D055815:Young Adult
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D005136:Eye Proteins; C490037:NRL protein, human