title: Novel nonsense and splice site mutations in CRB1 gene in two Japanese patients with early-onset retinal dystrophy.
abstract: OBJECTIVE
  To report novel mutations in the CRB1 gene in two patients with early-onset retinal dystrophy (EORD) and the longitudinal clinical course of EORD.
  
  
  METHODS
  The patients were two unrelated Japanese children. Standard ophthalmic examinations including perimetry, electroretinography, and optical coherence tomography were performed on both patients. Whole exomes of the patients and their nonsymptomatic parents were analyzed using a next-generation sequence (NGS) technique.
  
  
  RESULTS
  Patient 1 was noted to have esotropia and hyperopia at age 3. His decimal best-corrected visual acuity (BCVA) was 0.6 OD and 0.3 OS at age 6 with de-pigmentation of the retinal pigment epithelium (RPE). At age 19, his central vision was still preserved; however, numerous pigment granules were present in the retina. NGS analysis revealed a p.R632X nonsense and c.652 + 1_652 + 4delGTAA splice site mutations in the CRB1 gene. Patient 2 was noted to have hyperopia at age 3. His decimal BCVA at age 6 was 0.3 OD and 0.4 OS with de-pigmented RPE. The degree of retinal pigmentation was increased but his BCVA was good until the age of 14 years. NGS analysis revealed c.652 + 1_652 + 4delGTAA and c.652 + 1_652 + 2insT splice site mutations in the CRB1 gene.
  
  
  CONCLUSIONS
  The phenotypes of these novel mutations for EORD are typical of CRB1-associated EORD (LCA8). They were slowly progressive until the second decade of life.
authors.affiliation: Department of Ophthalmology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka, 589-8511, Japan, kuniyoshi-kazuki@umin.net.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kuniyoshi
authors.forename: Kazuho
authors.initials: K
authors.lastname: Ikeo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakuramoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Furuno
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Yoshitake
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hatsukawa
authors.forename: Akira
authors.initials: A
authors.lastname: Nakao
authors.forename: Kazushige
authors.initials: K
authors.lastname: Tsunoda
authors.forename: Shunji
authors.initials: S
authors.lastname: Kusaka
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
mesh_terms: D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D058499:Retinal Dystrophies / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D014794:Visual Fields
chemical_list: C448939:CRB1 protein, human; D018389:Codon, Nonsense; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins