THE CHARACTERIZATION OF RETINAL PHENOTYPE IN A FAMILY WITH C1QTNF5-RELATED LATE-ONSET RETINAL DEGENERATION

Purpose: To describe the clinical, spectral-domain optical coherence tomography and electrophysiological features of C1QTNF5-associated late-onset retinal degeneration in a molecularly confirmed pedigree. Methods: Five members of a family participated, and affected individuals (n = 4) underwent detailed ophthalmologic evaluation including fundus autofluorescence and spectral-domain optical coherence tomography imaging and electroretinography. Electrooculography was performed in three individuals. Results: The visual acuity was initially normal and worsened with time. Anterior segment abnormalities included peripupillary iris atrophy and long anterior insertion of zonules. Peripapillary atrophy, drusenoid deposition, and scalloped sectorial chorioretinal atrophy were observed in all older individuals (n = 3). Fundus autofluorescence demonstrated hypofluorescent areas corresponding to regions of chorioretinal atrophy. The spectral-domain optical coherence tomography demonstrated multiple areas of retinal pigment epithelium–Bruch membrane separation with intervening homogeneous deposition that corresponded to the drusenoid lesions and areas of chorioretinal atrophy. Electrooculography was normal in one individual and showed abnormally low dark trough measures in older individuals (n = 2). Electroretinography was normal in early stages (n = 1), but showed marked abnormalities in the rod system (n = 3), which was predominantly inner retinal (n = 2) in late stages. Conclusion: Late-onset retinal degeneration is a progressive degeneration, and anterior segment abnormalities present early. The widespread sub–retinal pigment epithelium deposition seen on spectral-domain optical coherence tomography in older individuals appears to be a characteristic in late stages. Electrooculography demonstrates abnormalities only in late stages of the disease.

[1]  M. Bach,et al.  ISCEV standard for clinical electro-oculography (2010 update) , 2017, Documenta ophthalmologica. Advances in ophthalmology.

[2]  D. Bartsch,et al.  A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration. , 2011, Human molecular genetics.

[3]  Michael Bach,et al.  ISCEV standard for clinical electro-oculography (2010 update) , 2011, Documenta Ophthalmologica.

[4]  S. J. Talks,et al.  Treatment of a choroidal neovascular membrane in a patient with late-onset retinal degeneration (L-ORD) with intravitreal Ranibizumab , 2010, Eye.

[5]  A. Webster,et al.  Clinical and biochemical effects of the E139K missense mutation in the TIMP3 gene, associated with Sorsby fundus dystrophy , 2009, Molecular vision.

[6]  M. Bach,et al.  ISCEV Standard for full-field clinical electroretinography (2008 update) , 2009, Documenta Ophthalmologica.

[7]  Aziz A. Khanifar,et al.  Drusen ultrastructure imaging with spectral domain optical coherence tomography in age-related macular degeneration. , 2008, Ophthalmology.

[8]  G. Holder,et al.  Biallelic mutation of BEST1 causes a distinct retinopathy in humans. , 2008, American journal of human genetics.

[9]  J. Heckenlively,et al.  CTRP5 is a membrane-associated and secretory protein in the RPE and ciliary body and the S163R mutation of CTRP5 impairs its secretion. , 2006, Investigative ophthalmology & visual science.

[10]  A. Lennon,et al.  Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5. , 2006, Human molecular genetics.

[11]  A. Wright,et al.  Long anterior lens zonules in late-onset retinal degeneration (L-ORD). , 2005, American journal of ophthalmology.

[12]  P. Sieving,et al.  Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation. , 2005, Investigative ophthalmology & visual science.

[13]  A. Bird,et al.  Acute zonal occult outer retinopathy: towards a set of diagnostic criteria , 2004, British Journal of Ophthalmology.

[14]  A. Cideciyan,et al.  Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration. , 2003, Human molecular genetics.

[15]  A. Cideciyan,et al.  Phenotypic marker for early disease detection in dominant late-onset retinal degeneration. , 2001, Investigative ophthalmology & visual science.

[16]  A. Cideciyan,et al.  Dominant late-onset retinal degeneration with regional variation of sub-retinal pigment epithelium deposits, retinal function, and photoreceptor degeneration. , 2000, Ophthalmology.

[17]  A. Milam,et al.  Accumulation of tissue inhibitor of metalloproteinases-3 in human eyes with Sorsby’s fundus dystrophy or retinitis pigmentosa , 1998, The British journal of ophthalmology.

[18]  T. Oshika,et al.  Anterior shift of zonular insertion onto the anterior surface of human crystalline lens with age. , 1998, Ophthalmology.

[19]  A. Cideciyan,et al.  Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration. , 1996, Investigative ophthalmology & visual science.

[20]  W R Green,et al.  Age-related Macular Degeneration Histopathologic Studies: The 1992 Lorenz E. Zimmerman Lecture , 1993, Ophthalmology.

[21]  D. Han,et al.  Electro-oculography in autosomal dominant vitreoretinochoroidopathy. , 1992, Archives of ophthalmology.

[22]  J. Marshall,et al.  Extensive subretinal pigment epithelial deposit in two brothers suffering from dominant retinitis pigmentosa , 1986, Graefe's Archive for Clinical and Experimental Ophthalmology.

[23]  M. Barricks.  Vitelliform lesions developing in normal fundi. , 1977, American journal of ophthalmology.

[24]  A. Wright,et al.  Late-onset retinal macular degeneration : clinical insights into an inherited retinal degeneration , 2009 .

[25]  P. Sieving,et al.  Autosomal dominant hemorrhagic macular dystrophy not associated with the TIMP3 gene. , 2000, Archives of ophthalmology.

[26]  G. Arden.  Newer electrodiagnostic techniques in ophthalmology. , 1967, Transactions of the ophthalmological societies of the United Kingdom.