PURPOSE: To ascertain the potential pathogenicity of a retinitis pigmentosa (RP)-causing RHO F45L allele in a family affected by congenital achromatopsia (ACHM). METHODS: Case series/observational study that included two patients with ACHM and 24 extended family members. Molecular genetic analysis was performed to identify RHO F45L carrier status in the family and a control population. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral domain optical coherence tomography (SD-OCT) was used to examine retinal lamination. Comprehensive clinical testing included acuity, color vision, and dilated fundus examination. Electroretinography was used to assess rod and cone function. RESULTS: Five carriers of the RHO F45L allele alone (24-80 years) and three carriers in combination with a heterozygous CNGA3 mutant allele (10-64 years) were all free of the classic symptoms and signs of RP. In heterozygous carriers of both mutations, SD-OCT showed normal retinal thickness and intact outer retinal layers; rod and cone densities were within normal limits on AOSLO. The phenotype in two individuals affected with ACHM and harboring the RHO F45L allele was indistinguishable from that previously reported for ACHM. CONCLUSIONS: The RHO F45L allele is not pathogenic in this large family; hence, the two ACHM patients would unlikely develop RP in the future. TRANSLATIONAL RELEVANCE: The combined approach of comprehensive molecular analysis of individual genomes and noninvasive cellular resolution retinal imaging enhances the current repertoire of clinical diagnostic tools, giving a substantial impetus to personalized medicine.
PURPOSE: To ascertain the potential pathogenicity of a retinitis pigmentosa (RP)-causing RHO F45L allele in a family affected by congenital achromatopsia (ACHM). METHODS: Case series/observational study that included two patients with ACHM and 24 extended family members. Molecular genetic analysis was performed to identify RHO F45L carrier status in the family and a control population. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral domain optical coherence tomography (SD-OCT) was used to examine retinal lamination. Comprehensive clinical testing included acuity, color vision, and dilated fundus examination. Electroretinography was used to assess rod and cone function. RESULTS: Five carriers of the RHO F45L allele alone (24-80 years) and three carriers in combination with a heterozygous CNGA3 mutant allele (10-64 years) were all free of the classic symptoms and signs of RP. In heterozygous carriers of both mutations, SD-OCT showed normal retinal thickness and intact outer retinal layers; rod and cone densities were within normal limits on AOSLO. The phenotype in two individuals affected with ACHM and harboring the RHO F45L allele was indistinguishable from that previously reported for ACHM. CONCLUSIONS: The RHO F45L allele is not pathogenic in this large family; hence, the two ACHM patients would unlikely develop RP in the future. TRANSLATIONAL RELEVANCE: The combined approach of comprehensive molecular analysis of individual genomes and noninvasive cellular resolution retinal imaging enhances the current repertoire of clinical diagnostic tools, giving a substantial impetus to personalized medicine.
Authors: Elizabeth P Rakoczy; Christina Kiel; Richard McKeone; François Stricher; Luis Serrano Journal: J Mol Biol Date: 2010-11-19 Impact factor: 5.469
Authors: Eliot L Berson; Bernard Rosner; Carol Weigel-DiFranco; Thaddeus P Dryja; Michael A Sandberg Journal: Invest Ophthalmol Vis Sci Date: 2002-09 Impact factor: 4.799
Authors: Alberta A H J Thiadens; Anneke I den Hollander; Susanne Roosing; Sander B Nabuurs; Renate C Zekveld-Vroon; Rob W J Collin; Elfride De Baere; Robert K Koenekoop; Mary J van Schooneveld; Tim M Strom; Janneke J C van Lith-Verhoeven; Andrew J Lotery; Norka van Moll-Ramirez; Bart P Leroy; L Ingeborgh van den Born; Carel B Hoyng; Frans P M Cremers; Caroline C W Klaver Journal: Am J Hum Genet Date: 2009-07-16 Impact factor: 11.025
Authors: C H Sung; C M Davenport; J C Hennessey; I H Maumenee; S G Jacobson; J R Heckenlively; R Nowakowski; G Fishman; P Gouras; J Nathans Journal: Proc Natl Acad Sci U S A Date: 1991-08-01 Impact factor: 11.205
Authors: S Kohl; T Marx; I Giddings; H Jägle; S G Jacobson; E Apfelstedt-Sylla; E Zrenner; L T Sharpe; B Wissinger Journal: Nat Genet Date: 1998-07 Impact factor: 38.330
Authors: Robert F Cooper; Adam M Dubis; Ashavini Pavaskar; Jungtae Rha; Alfredo Dubra; Joseph Carroll Journal: Biomed Opt Express Date: 2011-08-11 Impact factor: 3.732
Authors: Wayne I L Davies; Susan M Downes; Josephine K Fu; Morag E Shanks; Richard R Copley; Stefano Lise; Simon C Ramsden; Graeme C M Black; Kate Gibson; Russell G Foster; Mark W Hankins; Andrea H Németh Journal: Genet Med Date: 2012-07-12 Impact factor: 8.822
Authors: Shu Feng; Michael J Gale; Jonathan D Fay; Ambar Faridi; Hope E Titus; Anupam K Garg; Keith V Michaels; Laura R Erker; Dawn Peters; Travis B Smith; Mark E Pennesi Journal: Invest Ophthalmol Vis Sci Date: 2015-09 Impact factor: 4.799
Authors: Katie M Litts; Erica N Woertz; Niamh Wynne; Brian P Brooks; Alicia Chacon; Thomas B Connor; Deborah Costakos; Alina Dumitrescu; Arlene V Drack; Gerald A Fishman; William W Hauswirth; Christine N Kay; Byron L Lam; Michel Michaelides; Mark E Pennesi; Kimberly E Stepien; Sasha Strul; C Gail Summers; Joseph Carroll Journal: Transl Vis Sci Technol Date: 2021-05-03 Impact factor: 3.048
Authors: Tylor R Lewis; Camilla R Shores; Martha A Cady; Ying Hao; Vadim Y Arshavsky; Marie E Burns Journal: Sci Rep Date: 2020-05-05 Impact factor: 4.996