title: Genetic Analysis of the Rhodopsin Gene Identifies a Mosaic Dominant Retinitis Pigmentosa Mutation in a Healthy Individual.
abstract: OBJECTIVE
  Retinitis pigmentosa (RP) is a group of clinically and genetically heterogeneous hereditary retinal diseases that result in blindness due to photoreceptor degeneration. Mutations in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP) and are responsible for 16% to 35% of adRP cases in the Western population. Our purpose was to investigate the contribution of RHO to adRP in the Israeli and Palestinian populations.
  
  
  METHODS
  Thirty-two adRP families participated in the study. Mutation detection was performed by whole exome sequencing (WES) and Sanger sequencing of RHO exons. Fluorescence PCR reactions of serially diluted samples were used to predict the percentage of mosaic cells in blood samples.
  
  
  RESULTS
  Eight RHO disease-causing mutations were identified in nine families, with only one novel mutation, c.548-638dup91bp, identified in a family where WES failed to detect any causal variant. Segregation analysis revealed that the origin of the mutation is in a mosaic healthy individual carrying the mutation in approximately 13% of blood cells.
  
  
  CONCLUSIONS
  This is the first report of the mutation spectrum of a known adRP gene in the Israeli and Palestinian populations, leading to the identification of seven previously reported mutations and one novel mutation. Our study shows that RHO mutations are a major cause of adRP in this cohort and are responsible for 28% of adRP families. The novel mutation exhibits a unique phenomenon in which an unaffected individual is mosaic for an adRP-causing mutation.
authors.affiliation: Departments of Ophthalmology Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Avigail
authors.initials: A
authors.lastname: Beryozkin
authors.affiliation: Departments of Ophthalmology Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Levy
authors.affiliation: Departments of Ophthalmology Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Blumenfeld
authors.affiliation: Departments of Ophthalmology Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Segev
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Departments of Ophthalmology Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Namburi
authors.affiliation: Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Morad
authors.affiliation: Department of Ophthalmology, Clalit Health Services and Soroka University Medical Center, Beer-Sheva, Israel.
authors.forename: Libe
authors.initials: L
authors.lastname: Gradstein
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.affiliation: Departments of Ophthalmology Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.affiliation: Departments of Ophthalmology Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Sharon
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005006:Ethnicity; D005091:Exons; D005190:Family; D005260:Female; D005799:Genes, Dominant; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D009030:Mosaicism; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012016:Reference Values; D012174:Retinitis Pigmentosa / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004247:DNA; D012243:Rhodopsin