Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene

Samuel G. Jacobson, Artur V. Cideciyan, Yijun Huang, David B. Hanna, Carol L. Freund, Louisa M. Affatigato, Ronald E. Carr, Donald J. Zack, Edwin M. Stone, Roderick R. McInnes

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Abstract

PURPOSE. To define the phenotypes of retinal degenerations associated with mutations in the gene encoding CRX (cone-rod homeobox), a photoreceptor- specific transcription factor. METHODS. Heterozygotes with the E168 [Δ1 bp], E168 [Δ2 bp], or G217 [Δ1 bp] CRX gene mutation were studied clinically, with visual function tests, including rod and cone perimetry and electroretinography (ERG), and with optical coherence tomography (OCT). RESULTS. Clinical diagnoses included autosomal dominant cone-rod dystrophy in one family (E168 [Δ1 bp] mutation) and simplex Leber congenital amaurosis in two families (E168 [Δ2 bp], G217 [Δ1 bp] mutations). In the family with the E168 [Δ1 bp] mutation, two siblings had relatively mild disease expression in the third decade of life. The central retinas of these two patients had profound loss of rod and short wavelength cone function; long/middle wavelength cone thresholds were elevated at fixation, but there were greater paracentral than central abnormalities. Peripheral retinal dysfunction was evident by psychophysics and by maximum amplitude loss for rod- and cone- isolated ERG photoreceptor responses. OCT cross-sectional reflectance images showed decreased central retinal thickness consistent with photoreceptor loss. An additional member of this family (E168 [Δ1 bp] mutation) and two other patients (representing E168 [Δ2 bp] and G217 [Δ1 bp] mutations) had a severe phenotype with retina-wide loss of function and islands of function remaining only in the temporal periphery. CONCLUSIONS. Truncation mutations in CRX are associated with retinopathies that share phenotypic features but vary in disease severity. The disease mechanism could involve abnormal photoreceptor development compounded by a disturbance in the maintenance of photoreceptors in the mature retina.

Original languageEnglish (US)
Pages (from-to)2417-2426
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume39
Issue number12
StatePublished - Nov 1998
Externally publishedYes

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Retinal Degeneration
Vertebrate Photoreceptor Cells
Homeobox Genes
Mutation
Electroretinography
Retina
Optical Coherence Tomography
Leber Congenital Amaurosis
Psychophysics
Phenotype
Visual Field Tests
Heterozygote
Islands
Siblings
Transcription Factors
Maintenance

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Jacobson, S. G., Cideciyan, A. V., Huang, Y., Hanna, D. B., Freund, C. L., Affatigato, L. M., ... McInnes, R. R. (1998). Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene. Investigative Ophthalmology and Visual Science, 39(12), 2417-2426.

Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene. / Jacobson, Samuel G.; Cideciyan, Artur V.; Huang, Yijun; Hanna, David B.; Freund, Carol L.; Affatigato, Louisa M.; Carr, Ronald E.; Zack, Donald J.; Stone, Edwin M.; McInnes, Roderick R.

In: Investigative Ophthalmology and Visual Science, Vol. 39, No. 12, 11.1998, p. 2417-2426.

Research output: Contribution to journalArticle

Jacobson, SG, Cideciyan, AV, Huang, Y, Hanna, DB, Freund, CL, Affatigato, LM, Carr, RE, Zack, DJ, Stone, EM & McInnes, RR 1998, 'Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene', Investigative Ophthalmology and Visual Science, vol. 39, no. 12, pp. 2417-2426.
Jacobson SG, Cideciyan AV, Huang Y, Hanna DB, Freund CL, Affatigato LM et al. Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene. Investigative Ophthalmology and Visual Science. 1998 Nov;39(12):2417-2426.
Jacobson, Samuel G. ; Cideciyan, Artur V. ; Huang, Yijun ; Hanna, David B. ; Freund, Carol L. ; Affatigato, Louisa M. ; Carr, Ronald E. ; Zack, Donald J. ; Stone, Edwin M. ; McInnes, Roderick R. / Retinal degenerations with truncation mutations in the cone-rod homeobox (CRX) gene. In: Investigative Ophthalmology and Visual Science. 1998 ; Vol. 39, No. 12. pp. 2417-2426.
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abstract = "PURPOSE. To define the phenotypes of retinal degenerations associated with mutations in the gene encoding CRX (cone-rod homeobox), a photoreceptor- specific transcription factor. METHODS. Heterozygotes with the E168 [Δ1 bp], E168 [Δ2 bp], or G217 [Δ1 bp] CRX gene mutation were studied clinically, with visual function tests, including rod and cone perimetry and electroretinography (ERG), and with optical coherence tomography (OCT). RESULTS. Clinical diagnoses included autosomal dominant cone-rod dystrophy in one family (E168 [Δ1 bp] mutation) and simplex Leber congenital amaurosis in two families (E168 [Δ2 bp], G217 [Δ1 bp] mutations). In the family with the E168 [Δ1 bp] mutation, two siblings had relatively mild disease expression in the third decade of life. The central retinas of these two patients had profound loss of rod and short wavelength cone function; long/middle wavelength cone thresholds were elevated at fixation, but there were greater paracentral than central abnormalities. Peripheral retinal dysfunction was evident by psychophysics and by maximum amplitude loss for rod- and cone- isolated ERG photoreceptor responses. OCT cross-sectional reflectance images showed decreased central retinal thickness consistent with photoreceptor loss. An additional member of this family (E168 [Δ1 bp] mutation) and two other patients (representing E168 [Δ2 bp] and G217 [Δ1 bp] mutations) had a severe phenotype with retina-wide loss of function and islands of function remaining only in the temporal periphery. CONCLUSIONS. Truncation mutations in CRX are associated with retinopathies that share phenotypic features but vary in disease severity. The disease mechanism could involve abnormal photoreceptor development compounded by a disturbance in the maintenance of photoreceptors in the mature retina.",
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AU - Jacobson, Samuel G.

AU - Cideciyan, Artur V.

AU - Huang, Yijun

AU - Hanna, David B.

AU - Freund, Carol L.

AU - Affatigato, Louisa M.

AU - Carr, Ronald E.

AU - Zack, Donald J.

AU - Stone, Edwin M.

AU - McInnes, Roderick R.

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N2 - PURPOSE. To define the phenotypes of retinal degenerations associated with mutations in the gene encoding CRX (cone-rod homeobox), a photoreceptor- specific transcription factor. METHODS. Heterozygotes with the E168 [Δ1 bp], E168 [Δ2 bp], or G217 [Δ1 bp] CRX gene mutation were studied clinically, with visual function tests, including rod and cone perimetry and electroretinography (ERG), and with optical coherence tomography (OCT). RESULTS. Clinical diagnoses included autosomal dominant cone-rod dystrophy in one family (E168 [Δ1 bp] mutation) and simplex Leber congenital amaurosis in two families (E168 [Δ2 bp], G217 [Δ1 bp] mutations). In the family with the E168 [Δ1 bp] mutation, two siblings had relatively mild disease expression in the third decade of life. The central retinas of these two patients had profound loss of rod and short wavelength cone function; long/middle wavelength cone thresholds were elevated at fixation, but there were greater paracentral than central abnormalities. Peripheral retinal dysfunction was evident by psychophysics and by maximum amplitude loss for rod- and cone- isolated ERG photoreceptor responses. OCT cross-sectional reflectance images showed decreased central retinal thickness consistent with photoreceptor loss. An additional member of this family (E168 [Δ1 bp] mutation) and two other patients (representing E168 [Δ2 bp] and G217 [Δ1 bp] mutations) had a severe phenotype with retina-wide loss of function and islands of function remaining only in the temporal periphery. CONCLUSIONS. Truncation mutations in CRX are associated with retinopathies that share phenotypic features but vary in disease severity. The disease mechanism could involve abnormal photoreceptor development compounded by a disturbance in the maintenance of photoreceptors in the mature retina.

AB - PURPOSE. To define the phenotypes of retinal degenerations associated with mutations in the gene encoding CRX (cone-rod homeobox), a photoreceptor- specific transcription factor. METHODS. Heterozygotes with the E168 [Δ1 bp], E168 [Δ2 bp], or G217 [Δ1 bp] CRX gene mutation were studied clinically, with visual function tests, including rod and cone perimetry and electroretinography (ERG), and with optical coherence tomography (OCT). RESULTS. Clinical diagnoses included autosomal dominant cone-rod dystrophy in one family (E168 [Δ1 bp] mutation) and simplex Leber congenital amaurosis in two families (E168 [Δ2 bp], G217 [Δ1 bp] mutations). In the family with the E168 [Δ1 bp] mutation, two siblings had relatively mild disease expression in the third decade of life. The central retinas of these two patients had profound loss of rod and short wavelength cone function; long/middle wavelength cone thresholds were elevated at fixation, but there were greater paracentral than central abnormalities. Peripheral retinal dysfunction was evident by psychophysics and by maximum amplitude loss for rod- and cone- isolated ERG photoreceptor responses. OCT cross-sectional reflectance images showed decreased central retinal thickness consistent with photoreceptor loss. An additional member of this family (E168 [Δ1 bp] mutation) and two other patients (representing E168 [Δ2 bp] and G217 [Δ1 bp] mutations) had a severe phenotype with retina-wide loss of function and islands of function remaining only in the temporal periphery. CONCLUSIONS. Truncation mutations in CRX are associated with retinopathies that share phenotypic features but vary in disease severity. The disease mechanism could involve abnormal photoreceptor development compounded by a disturbance in the maintenance of photoreceptors in the mature retina.

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