title: Genotype-phenotype correlations in Bothnia dystrophy caused by RLBP1 gene sequence variations.
abstract: OBJECTIVE
  To evaluate phenotypes caused by different RLBP1 mutations in autosomal recessive retinitis pigmentosa of Bothnia type.
  
  
  METHODS
  Compound heterozygotes for mutations in the RLBP1 gene [c.677T>A]+[c.700C>T] (p.M226K+p.R234W), n = 10, aged 7-84 years, and homozygotes c.677T>A (p.M226K), n = 2, aged 63 and 73 years, were studied using visual acuity (VA), low-contrast VA, visual fields (VFs) and optical coherence tomography (OCT). Retrospective VA and VFs, standardized dark adaptation and full-field electroretinograms (ERGs) were analysed and prolonged dark adaptometry and ERG (at 24 hr) were performed.
  
  
  RESULTS
  Progressive decline of VA and VF areas was age-dependent. Retinal degenerative maculopathy, peripheral degenerative changes and retinitis punctata albescens (RPA) were present. Early retinal thinning in the central foveal, foveal (Ø 1 mm), and inner ring (Ø 3 mm) in the macular region, with homogenous, high-reflectance RPA changes, was visualized in and adjacent to the retinal pigment epithelium/choriocapillaris using OCT. Reduced dark adaptation and affected ERGs were present in all ages. Prolonged dark adaptation and ERG (at 24 hr), an increase in final threshold, and ERG rod and mixed rod/cone responses were found.
  
  
  CONCLUSIONS
  The two RLBP1 genotypes presented a phenotypical and electrophysiological expression of progressive retinal disease similar to that previously described in homozygotes for the c.700C>T (p.R234W) RLBP1 mutation. The uniform phenotypical expression of RLBP1 mutations is relevant information for the disease and of importance in planning future treatment strategies.
authors.affiliation: Department of Clinical Sciences/Ophthalmology, University of Umeå, Umeå, Sweden. marie.burstedt@ophthal.umu.se
authors.forename: Marie
authors.initials: M
authors.lastname: Burstedt
authors.forename: Frida
authors.initials: F
authors.lastname: Jonsson
authors.forename: Linda
authors.initials: L
authors.lastname: Köhn
authors.forename: Magnus
authors.initials: M
authors.lastname: Burstedt
authors.forename: Markus
authors.initials: M
authors.lastname: Kivitalo
authors.forename: Irina
authors.initials: I
authors.lastname: Golovleva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D030541:Databases, Genetic / Q000706:statistics & numerical data*; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D012172:Retinaldehyde; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C020932:11-cis-retinal-binding protein; D002352:Carrier Proteins; D012172:Retinaldehyde