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A new mutation in the RP1L1 gene in a patient with occult macular dystrophy associated with a depolarizing pattern of focal macular electroretinograms.

Kabuto T, Takahashi H, Goto-Fukuura Y, Igarashi T, Akahori M, Kameya S, Iwata T, Mizota A, Yamaki K, Miyake Y, Takahashi H - Mol. Vis. (2012)

Bottom Line: The variant c.3596 C>G in exon 4 resulted in the substitution of cysteine for serine at amino acid position 1199.The serine at position 1199 is well conserved among the RP1L1 family in other species.We have demonstrated in a Japanese patient the possibility that sporadic OMD may also be caused by an RP1L1 mutation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.

ABSTRACT

Purpose: To determine whether a mutation in the RP1-like protein 1 (RP1L1) gene is present in a Japanese patient with sporadic occult macular dystrophy (OMD) and to examine the characteristics of focal macular electroretinograms (ERGs) of the patient with genetically identified OMD.

Methods: An individual with OMD underwent detailed ophthalmic clinical evaluations including focal macular ERGs. Mutation screening of all coding regions and flanking intron sequences of the RP1L1 gene were performed with DNA sequencing analysis in this case with OMD.

Results: A new RP1L1 mutation (c.3596 C>G in exon 4) was identified. The variant c.3596 C>G in exon 4 resulted in the substitution of cysteine for serine at amino acid position 1199. The serine at position 1199 is well conserved among the RP1L1 family in other species. Four out of five computational assessment tools predicted that this mutation is damaging to the protein function. This mutation was not present in 294 control alleles. The waveform of focal macular ERGs recorded from the patient with OMD had a depolarizing pattern, simulating the ERG waveforms observed after the hyperpolarizing bipolar cell activity is blocked.

Conclusions: We have demonstrated in a Japanese patient the possibility that sporadic OMD may also be caused by an RP1L1 mutation. The waveform of focal macular ERGs elicited from the OMD patient with the RP1L1 mutation showed a depolarizing pattern. This characteristic is the same as reported for the focal macular ERGs of OMD.

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Related in: MedlinePlus

Results of focal macular electroretinograms (ERGs) and multifocal ERGs. Focal macular ERGs and oscillatory potentials recorded from a normal subject and this case are shown (top). The amplitude of the a-wave of this case was severely reduced, and the plateau region was significantly elevated (arrows). The topographic map and the local responses of multifocal ERGs recorded from the normal subject and this case are shown (bottom). The amplitudes in the foveal area were severely reduced in this case.
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f4: Results of focal macular electroretinograms (ERGs) and multifocal ERGs. Focal macular ERGs and oscillatory potentials recorded from a normal subject and this case are shown (top). The amplitude of the a-wave of this case was severely reduced, and the plateau region was significantly elevated (arrows). The topographic map and the local responses of multifocal ERGs recorded from the normal subject and this case are shown (bottom). The amplitudes in the foveal area were severely reduced in this case.

Mentions: A severe reduction in the a-waves of the focal macular ERGs was found in this case (Figure 4). Although the b-waves were large, their shapes were abnormal. The b-waves rose to a peak, and the potential was maintained longer than normal. The plateau region of the b-wave was significantly elevated above the baseline potential (Figure 4, arrow). To analyze this characteristic, we quantified the potentials at 70 ms after the stimulus was turned on, and the recovery time of the descending slope of b-wave to the baseline from the peak of the b-wave. We calculated the 95% confidence intervals (CI) for the amplitudes of the a-waves and b-waves, the implicit times of the a-waves and b-waves, the potentials at 70 ms after the stimulus turns on, and the time of the recovery of the b-waves to the baseline obtained from the normal controls (Figure 5). Among these six parameters, the amplitudes of the a-waves, the implicit times of the b-waves, the potentials at 70 ms after the stimulus was turned on, and the time of the recovery of the descending slope of the b-wave to the baseline obtained from both eyes of this case were outside the range of the standard deviation and the 95% CI of the normal controls (Figure 5). Especially, the amplitudes of the a-waves, the potentials at 70 ms after the stimulus was turned on, and the time of the recovery of the descending slope of the b-wave to the baseline obtained from this case were severely affected. The amplitudes of the mfERGs in the foveal area were severely reduced in this case (Figure 4).


A new mutation in the RP1L1 gene in a patient with occult macular dystrophy associated with a depolarizing pattern of focal macular electroretinograms.

Kabuto T, Takahashi H, Goto-Fukuura Y, Igarashi T, Akahori M, Kameya S, Iwata T, Mizota A, Yamaki K, Miyake Y, Takahashi H - Mol. Vis. (2012)

Results of focal macular electroretinograms (ERGs) and multifocal ERGs. Focal macular ERGs and oscillatory potentials recorded from a normal subject and this case are shown (top). The amplitude of the a-wave of this case was severely reduced, and the plateau region was significantly elevated (arrows). The topographic map and the local responses of multifocal ERGs recorded from the normal subject and this case are shown (bottom). The amplitudes in the foveal area were severely reduced in this case.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351429&req=5

f4: Results of focal macular electroretinograms (ERGs) and multifocal ERGs. Focal macular ERGs and oscillatory potentials recorded from a normal subject and this case are shown (top). The amplitude of the a-wave of this case was severely reduced, and the plateau region was significantly elevated (arrows). The topographic map and the local responses of multifocal ERGs recorded from the normal subject and this case are shown (bottom). The amplitudes in the foveal area were severely reduced in this case.
Mentions: A severe reduction in the a-waves of the focal macular ERGs was found in this case (Figure 4). Although the b-waves were large, their shapes were abnormal. The b-waves rose to a peak, and the potential was maintained longer than normal. The plateau region of the b-wave was significantly elevated above the baseline potential (Figure 4, arrow). To analyze this characteristic, we quantified the potentials at 70 ms after the stimulus was turned on, and the recovery time of the descending slope of b-wave to the baseline from the peak of the b-wave. We calculated the 95% confidence intervals (CI) for the amplitudes of the a-waves and b-waves, the implicit times of the a-waves and b-waves, the potentials at 70 ms after the stimulus turns on, and the time of the recovery of the b-waves to the baseline obtained from the normal controls (Figure 5). Among these six parameters, the amplitudes of the a-waves, the implicit times of the b-waves, the potentials at 70 ms after the stimulus was turned on, and the time of the recovery of the descending slope of the b-wave to the baseline obtained from both eyes of this case were outside the range of the standard deviation and the 95% CI of the normal controls (Figure 5). Especially, the amplitudes of the a-waves, the potentials at 70 ms after the stimulus was turned on, and the time of the recovery of the descending slope of the b-wave to the baseline obtained from this case were severely affected. The amplitudes of the mfERGs in the foveal area were severely reduced in this case (Figure 4).

Bottom Line: The variant c.3596 C>G in exon 4 resulted in the substitution of cysteine for serine at amino acid position 1199.The serine at position 1199 is well conserved among the RP1L1 family in other species.We have demonstrated in a Japanese patient the possibility that sporadic OMD may also be caused by an RP1L1 mutation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.

ABSTRACT

Purpose: To determine whether a mutation in the RP1-like protein 1 (RP1L1) gene is present in a Japanese patient with sporadic occult macular dystrophy (OMD) and to examine the characteristics of focal macular electroretinograms (ERGs) of the patient with genetically identified OMD.

Methods: An individual with OMD underwent detailed ophthalmic clinical evaluations including focal macular ERGs. Mutation screening of all coding regions and flanking intron sequences of the RP1L1 gene were performed with DNA sequencing analysis in this case with OMD.

Results: A new RP1L1 mutation (c.3596 C>G in exon 4) was identified. The variant c.3596 C>G in exon 4 resulted in the substitution of cysteine for serine at amino acid position 1199. The serine at position 1199 is well conserved among the RP1L1 family in other species. Four out of five computational assessment tools predicted that this mutation is damaging to the protein function. This mutation was not present in 294 control alleles. The waveform of focal macular ERGs recorded from the patient with OMD had a depolarizing pattern, simulating the ERG waveforms observed after the hyperpolarizing bipolar cell activity is blocked.

Conclusions: We have demonstrated in a Japanese patient the possibility that sporadic OMD may also be caused by an RP1L1 mutation. The waveform of focal macular ERGs elicited from the OMD patient with the RP1L1 mutation showed a depolarizing pattern. This characteristic is the same as reported for the focal macular ERGs of OMD.

Show MeSH
Related in: MedlinePlus