title: Whole-exome sequencing identifies a novel homozygous frameshift mutation in the PROM1 gene as a causative mutation in two patients with sporadic retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP) refers to a heterogeneous group of inherited retinal diseases caused by the loss of photoreceptors. The present study aimed to identify the gene mutations responsible for RP in two patients diagnosed with sporadic RP using next-generation sequencing technology. For this purpose, two patients with sporadic RP and family members (namely parents and siblings) were recruited into this study and underwent a complete ophthalmological assessment. Whole-exome sequencing (WES) was performed on genomic DNA samples isolated from peripheral leukocytes which had been obtained from the two patients diagnosed with sporadic RP. WES data were annotated and filtered against four public databases and one in-house database. Subsequently, Sanger sequencing was performed in order to determine whether any of the candidate variants co-segregated with the disease phenotype in the families. A homozygous frameshift mutation, c.1445dupT (p.F482fs) in exon 12 of the PROM1 gene (MIM: 604365), satisfied a recessive inheritance model and showed complete co-segregation of the mutation with the disease phenotype in the families. The same mutation was not detected in the 200 ethnically-matched control samples by Sanger sequencing. The novel homozygous mutation c.1445dupT (p.F482fs) in the PROM1 gene was identified as a causative mutation for RP. Thus, the identification of this mutation has further expanded the existing spectrum of PROM1 mutations in patients with RP, thereby assisting in the molecular diagnosis of RP and enhancing our understanding of genotype-phenotype correlations in order to provide effective genetic counseling.
authors.affiliation: Department of Ophthalmology, Hospital of The University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China.
authors.forename: Sanmei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Gynecology and Obstetrics, Hospital of The University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Gynecology and Obstetrics, Hospital of The University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yue
authors.affiliation: Department of Gynecology and Obstetrics, Hospital of The University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Peng
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China.
authors.forename: Biyuan
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China.
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D059472:Exome; D005190:Family; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D056726:Genetic Association Studies; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology
chemical_list: D000071916:AC133 Antigen; C000606023:PROM1 protein, human