title: Association of NR2E3 but not NRL mutations with retinitis pigmentosa in the Chinese population.
abstract: Purpose. Mutations in the NR2E3 and NRL genes have been implicated in both autosomal dominant and autosomal recessive retinitis pigmentosa (RP). In this study, the mutation profiles of these two genes were investigated in Chinese RP patients. Methods. In 172 RP patients and 360 normal control subjects (180 from Hong Kong and 180 from Beijing), the coding exons and the exon-intron boundaries of NR2E3 and NRL were screened by direct DNA sequencing after PCR. Association analysis was performed for common single-nucleotide polymorphisms (SNPs), whereas in silico programs were used for analysis of rare missense variants. Results. In NR2E3, 14 novel sequence changes have been identified. Two missense variants, p.G56R and p.V118M, were exclusively found in RP patients with frequencies at 1.2% (2/172) and 1.7% (3/172), respectively. All five patients were found to be heterozygous for these two mutations. Computational analysis suggested functional defects on the NR2E3 protein, indicating disease-causing roles. The p.E121K variant of NR2E3, which reportedly caused enhanced S-cone syndrome (ESCS) in Caucasians, was found concurrently in RP patients (13.4%) and control subjects from Hong Kong (10.5%) and Beijing (12.8%). In NRL, six novel sequence changes were identified, none of them associated with RP. Conclusions. In this study, NR2E3 mutations (p.G56R, p.V118M) were found to be responsible for approximately 2.9% of overall RP in Chinese patients, comparable to the contributions of RHO and RP1 mutations. The p.E121K in NR2E3 is a common SNP in the Chinese, suggesting another genetic or environmental factor is involved in its causative role in ESCS in Caucasians.
authors.affiliation: Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Li Jia
authors.initials: LJ
authors.lastname: Chen
authors.forename: Sylvia W Y
authors.initials: SW
authors.lastname: Chiang
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.forename: Timothy Y Y
authors.initials: TY
authors.lastname: Lai
authors.forename: Carmen K M
authors.initials: CK
authors.lastname: Chan
authors.forename: Ningli
authors.initials: N
authors.lastname: Wang
authors.forename: Dennis S C
authors.initials: DS
authors.lastname: Lam
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D005136:Eye Proteins; C403073:NR2E3 protein, human; C490037:NRL protein, human; D057093:Orphan Nuclear Receptors