Identification of a novel homozygous nonsense mutation in EYS in a Chinese family with autosomal recessive retinitis pigmentosa

Abstract

BackgroundRetinitis pigmentosa is the most important hereditary retinal degenerative disease, which has a high degree of clinical and genetic heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal recessive (arRP), but the gene(s) causing arRP in most families has yet to be identified. The purpose of this study is to identify the genetic basis of severe arRP in a consanguineous Chinese family.MethodsLinkage and haplotype analyses were used to define the chromosomal location of the pathogenic gene in the Chinese arRP family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of EYS was used to determine the disease-causing mutation, and to demonstrate that the mutation co-segregates with the disease in the family.ResultsA single nucleotide substitution of G to T at nucleotide 5506 of EYS was identified in the Chinese arRP family. This change caused a substitution of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and resulted in a premature truncated EYS protein with 1,835 amino acids. Three affected siblings in the family were homozygous for the p.E1836X mutation, while the other unaffected family members carried one mutant allele and one normal EYS allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal controls.ConclusionsThe EYS gene is a recently identified disease-causing gene for retinitis pigmentosa, and encodes the orthologue of Drosophila spacemaker. To date, there are only eight mutations in EYS that have been identified to cause arRP. Here we report one novel homozygous nonsense mutation of EYS in a consanguineous Chinese arRP family. Our study represents the first independent confirmation that mutations in EYS cause arRP. Additionally, this is the first EYS mutation identified in the Chinese population.

Targeted Next-generation Sequencing Reveals Novel EYS Mutations in Chinese Families with Autosomal Recessive Retinitis Pigmentosa

“…Mutations in the EYS gene are recognized as major causes for ARRP in multiple ethnic groups 7 8 9 10 11 . Reportedly, EYS mutations account for nearly 5% of ARRP patients with western European ancestry 12 , while 15.9% of ARRP patients in the Spanish population 9 .…”

EYSmutation update: In silico assessment of 271 reported and 26 novel variants in patients with retinitis pigmentosa

“…In total, we collected information of 377 RP patients described in 43 papers (Abd El‐Aziz et al., ; Abd El‐Aziz et al., ; Abu‐Safieh et al., ; Arai et al., ; Audo et al., ; Audo et al., ; Bandah‐Rozenfeld et al., ; Barragan et al., ; Beryozkin et al., ; Bonilha et al., ; Chen, et al., ; Collin et al., ; Consugar et al., ; Di et al., ; Eisenberger et al., ; Ge et al., ; Glockle et al., ; Gonzalez‐del Pozo et al., ; Gu, Tian, Chen, & Zhao, ; Habibi, et al., ; Haer‐Wigman et al., ; Hashmi, et al., ; Hosono et al., ; Huang et al., ; Huang et al., ; Iwanami, Oshikawa, Nishida, Nakadomari, & Kato, ; Jinda et al., ; Kastner et al., ; Katagiri et al., ; Khan et al., ; Littink et al., ; Littink et al., ; Neveling et al., ; Nishiguchi et al., ; Oishi et al., ; O'Sullivan et al., ; Perez‐Carro et al., ; Pieras et al., ; Pierrottet et al., ; Siemiatkowska et al., ; Suto et al., ; Xu, et al., ; Yoon et al., ), in which 630 alleles with EYS variants were reported. In addition, we identified 26 novel variants found in 36 index patients that were not published previously (Table ).…”

Ablation of EYS in zebrafish causes mislocalisation of outer segment proteins, F-actin disruption and cone-rod dystrophy

“…EYS , which spans more than 2 Mb within the RP25 locus (6q12), consists of 43 exons and encodes a 3165 amino acid protein localised in the outer segment of the photoreceptor23. Mutations in EYS are recognised as a major cause for autosomal recessive retinitis pigmentosa (arRP)4567, accounting for 5–18% arRP patients in different populations489, and have also been identified in patients with autosomal recessive cone-rod dystrophy (arCRD)1011. So far, about 100 EYS mutations, predominantly truncation mutations along with some missense mutations have been reported234567891011121314151617.…”