A Rare Form of Retinal Dystrophy Caused by Hypomorphic Nonsense Mutations in CEP290
Abstract
:1. Introduction
2. Material and Methods
2.1. Clinical Examination
2.2. Genetic Testing
2.3. Sequence Analysis of the CEP290 Gene
2.4. Analysis of Hypomorphic Character of the c.4723A>T Variant
3. Results
3.1. Clinical Findings
3.2. Genetic Analysis
3.3. Analysis of the Hypomorphic Character of c.4723A>T
4. Discussion and Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Patient ID | II-1 | II-2 |
---|---|---|
Sex | Female | Male |
Age at diagnosis | 3 | 2 |
Age recent examination | 46 | 45 |
Nystagmus | Present | Present |
Visual acuity RE | 20/100 | 20/80 |
Visual acuity LE | 20/100 | 20/160 |
Refraction | RE: +1.25–2.25 × 19; LE: −0.25–3.00 × 170 | RE: −14.25–1.75 × 5; LE: −10.25–2.25 × 155 |
Lens | Clear | Clear |
Fundus | Pink optic discs, mildly attenuated arterioles, coarse-grained aspect RPE posterior pole and mid-periphery superior quadrants, faintly recognizable foveola reflex BE with subtle indication for bull’s eye-like maculopathy, RPE atrophy in far periphery of superior quadrants, RPE atrophy in mid- and far periphery of inferior quadrants with scarce bone-spicule pigmentations | Pink, myopic optic discs, mildly attenuated arterioles, subtle RPE alterations macula RE, ring-shaped atrophy surrounding the fovea LE, faintly recognizable foveola reflex BE, perimacular RPE atrophy, mild RPE changes superior quadrants, RPE atrophy inferior quadrants with bone-spicule pigmentations |
Fundus autofluorescence | Relatively normal | Double hyperautofluorescent ring, hypoautofluorescent spots along and inferior to the inferior vascular arcade BE, and in macula LE |
OCT | Failed | No discernible photoreceptor complexes at the macula, but present at the peripheral part of the scan. |
Color vision (Panel D-15) | Saturated: normal Desaturated: minor errors RE, multiple errors LE, no specific axis | RE: de- and saturated: multiple errors mainly in tritan axis LE: failed |
Visual field (Goldmann) | Radius < 100 | Altitudinal defect BE, partially including the center RE, central scotoma LE |
ERG Dark adapted | Mildly reduced isolated rod responses with significantly reduced ‘mixed’ responses | Significantly reduced isolated rod and ‘mixed’ responses |
ERG Light adapted | Non-recordable | Non-recordable |
Miscellaneous | Anorexia, depressions, followed by the diagnosis of schizofrenia at age 29 | None |
First Allele | Second Allele | |||||||
---|---|---|---|---|---|---|---|---|
Sample ID | Diagnosis | DNA Variant | Predicted Protein Variant | Predicted Proteins Based on RNA Study | DNA Variant | Predicted Protein Variant | Predicted Proteins Based on RNA Study | Ref. |
Compound heterozygous | ||||||||
Family A | OT | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] # | c.451C>T | p.(Arg151*) | p.[Arg151*, Leu148_Glu165del, Leu148_Lys172del] | This study |
809 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.1709C>G | p.(Ser570*) | ND | [10] |
LCA-6 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.2991+1655A>G | p.(Cys998*) | p.[Cys998*, =] $ | [41] |
LCA-7 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.2991+1655A>G | p.(Cys998*) | p.[Cys998*, =] | [41] |
LCA-8 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.2991+1655A>G | p.(Cys998*) | p.[Cys998*, =] | [41] |
LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.2991+1655A>G | p.(Cys998*) | p.[Cys998*, =] | [42] | |
LCA-24 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4696G>C | p.(Ala1556Pro) | ND | [41] |
COR031/CORS1 | CORS | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4393C>T | p.(Arg1465*) | ND | [10,43] |
SLS-2 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4393C>T | p.(Arg1465*) | ND | [41] |
SLS-3 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4393C>T | p.(Arg1465*) | ND | [41] |
F283-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.1984C>T | p.(Gln662*) | ND | [44] |
A3100-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.1987A>T | p.(Lys663*) | ND | [44] |
A1210-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.3802C>T | p.(Gln1268*) | ND | [44] |
F118-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4452_4455delAGAA | p.(Lys1484Asnfs*4) | ND | [44] |
A1712-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.1189+1A>G | p.(?) | ND | [44] |
Homozygous | ||||||||
1 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [46] |
2 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [46] |
738 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
848 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
258 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
419 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
LEP | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
LCA-25 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [41] |
623 | JBTS+retina | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
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Share and Cite
Roosing, S.; Cremers, F.P.M.; Riemslag, F.C.C.; Zonneveld-Vrieling, M.N.; Talsma, H.E.; Klessens-Godfroy, F.J.M.; Den Hollander, A.I.; Van den Born, L.I. A Rare Form of Retinal Dystrophy Caused by Hypomorphic Nonsense Mutations in CEP290. Genes 2017, 8, 208. https://doi.org/10.3390/genes8080208
Roosing S, Cremers FPM, Riemslag FCC, Zonneveld-Vrieling MN, Talsma HE, Klessens-Godfroy FJM, Den Hollander AI, Van den Born LI. A Rare Form of Retinal Dystrophy Caused by Hypomorphic Nonsense Mutations in CEP290. Genes. 2017; 8(8):208. https://doi.org/10.3390/genes8080208
Chicago/Turabian StyleRoosing, Susanne, Frans P. M. Cremers, Frans C. C. Riemslag, Marijke N. Zonneveld-Vrieling, Herman E. Talsma, Francoise J. M. Klessens-Godfroy, Anneke I. Den Hollander, and L. Ingeborgh Van den Born. 2017. "A Rare Form of Retinal Dystrophy Caused by Hypomorphic Nonsense Mutations in CEP290" Genes 8, no. 8: 208. https://doi.org/10.3390/genes8080208