title: Targeted next-generation sequencing reveals novel EYS mutations in Chinese families with autosomal recessive retinitis pigmentosa.
abstract: EYS mutations demonstrate great genotypic and phenotypic varieties, and are one of the major causes for patients with autosomal recessive retinitis pigmentosa (ARRP). Here, we aim to determine the genetic lesions with phenotypic correlations in two Chinese families with ARRP. Medical histories and ophthalmic documentations were obtained from all participants from the two pedigrees. Targeted next-generation sequencing (NGS) on 189 genes was performed to screen for RP causative mutations in the two families. Two biallelic mutations in EYS, p.[R164*];[C2139Y] and p.[W2640*];[F2954S], were identified in the two families, respectively. EYS p.R164* and p.F2954S are novel alleles associated with RP, while p.C2139Y and p.W2640* are known mutations. Crystal structure modeling on the protein eyes shut homolog encoded by the EYS gene revealed abnormal hydrogen bonds generated by p.C2139Y and p.F2954S, which would likely affect the solubility and cause significant structural changes of the two mutated proteins. In conclusion, our study expands the genotypic spectrums for EYS mutations, and may provide novel insights into the relevant pathogenesis for RP. We also demonstrate targeted NGS approach as a valuable tool for genetic diagnosis.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
authors.forename: Xunlun
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Ophthalmology, School of Medicine, Henan Polytechnic University, Henan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Ophthalmology, School of Medicine, Henan Polytechnic University, Henan, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
authors.forename: Zili
authors.initials: Z
authors.lastname: Li
authors.affiliation: Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Li
authors.affiliation: Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
authors.forename: Yani
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Ningxia Eye Hospital, Ningxia People's Hospital, Ningxia, China.
authors.forename: Weining
authors.initials: W
authors.lastname: Rong
authors.affiliation: Tianjin Medical University, Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, China.
authors.forename: Kanxing
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People; D002681:China; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology
chemical_list: C533105:EYS protein, human; D005136:Eye Proteins