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Identification of a novel nonsense mutation in RP1 that causes autosomal recessive retinitis pigmentosa in an Indonesian family.

Siemiatkowska AM, Astuti GD, Arimadyo K, den Hollander AI, Faradz SM, Cremers FP, Collin RW - Mol. Vis. (2012)

Bottom Line: Unaffected family members either carried two wild-type alleles or were heterozygous carriers of the mutation.Most of the previously reported RP1 mutations are inherited in an autosomal dominant mode, and appear to cluster in exon 4.Here, we identified a novel homozygous p.R338* mutation in exon 4 of RP1, and speculate on the mutational mechanisms of different RP1 mutations underlying dominant and recessive RP.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

ABSTRACT

Purpose: The purpose of this study was to identify the underlying molecular genetic defect in an Indonesian family with three affected individuals who had received a diagnosis of retinitis pigmentosa (RP).

Methods: Clinical evaluation of the family members included measuring visual acuity and fundoscopy, and assessing visual field and color vision. Genomic DNA of the three affected individuals was analyzed with Illumina 700k single nucleotide polymorphism (SNP) arrays, and homozygous regions were identified using PLINK software. Mutation analysis was performed with sequence analysis of the retinitis pigmentosa 1 (RP1) gene that resided in one of the homozygous regions. The frequency of the identified mutation in the Indonesian population was determined with TaqI restriction fragment length polymorphism analysis.

Results: A novel homozygous nonsense mutation in exon 4 of the RP1 gene, c.1012C>T (p.R338*), was identified in the proband and her two affected sisters. Unaffected family members either carried two wild-type alleles or were heterozygous carriers of the mutation. The mutation was not present in 184 Indonesian control samples.

Conclusions: Most of the previously reported RP1 mutations are inherited in an autosomal dominant mode, and appear to cluster in exon 4. Here, we identified a novel homozygous p.R338* mutation in exon 4 of RP1, and speculate on the mutational mechanisms of different RP1 mutations underlying dominant and recessive RP.

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Related in: MedlinePlus

Fundus photographs of affected individuals. Fundus photographs of the right eye from affected individual II:4 A: affected individual II:6 B: affected individual II:7 C: and the unaffected father I:1 D: who carries the mutation heterozygously. The ages at the time of investigation of individuals II:4, II:6, and II:7 were 36, 28, and 26, respectively. Fundus examination of the affected individuals revealed typical features of retinitis pigmentosa, bone spicule-like pigmentations were found in the mid periphery of retina (indicated with arrows), and retinal vessels were attenuated (arrowheads).
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f2: Fundus photographs of affected individuals. Fundus photographs of the right eye from affected individual II:4 A: affected individual II:6 B: affected individual II:7 C: and the unaffected father I:1 D: who carries the mutation heterozygously. The ages at the time of investigation of individuals II:4, II:6, and II:7 were 36, 28, and 26, respectively. Fundus examination of the affected individuals revealed typical features of retinitis pigmentosa, bone spicule-like pigmentations were found in the mid periphery of retina (indicated with arrows), and retinal vessels were attenuated (arrowheads).

Mentions: All three affected individuals (II:4, II:6, and II:7) presented with night blindness that started at an early age. They displayed gradual constriction of their visual field and low visual acuity. Fundus examination revealed typical RP including the bone spicule-like pigment deposits in the mid-peripheral retina and narrowing of the retinal vessels (Figure 2). The unaffected sibling (II:2) did not experience night blindness or any other symptoms of RP. Apart from slightly decreased visual acuity, which is probably age-related, the proband's father (I:1) did not display any ophthalmological symptoms either. The clinical data for all participating individuals are summarized in Table 2.


Identification of a novel nonsense mutation in RP1 that causes autosomal recessive retinitis pigmentosa in an Indonesian family.

Siemiatkowska AM, Astuti GD, Arimadyo K, den Hollander AI, Faradz SM, Cremers FP, Collin RW - Mol. Vis. (2012)

Fundus photographs of affected individuals. Fundus photographs of the right eye from affected individual II:4 A: affected individual II:6 B: affected individual II:7 C: and the unaffected father I:1 D: who carries the mutation heterozygously. The ages at the time of investigation of individuals II:4, II:6, and II:7 were 36, 28, and 26, respectively. Fundus examination of the affected individuals revealed typical features of retinitis pigmentosa, bone spicule-like pigmentations were found in the mid periphery of retina (indicated with arrows), and retinal vessels were attenuated (arrowheads).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472925&req=5

f2: Fundus photographs of affected individuals. Fundus photographs of the right eye from affected individual II:4 A: affected individual II:6 B: affected individual II:7 C: and the unaffected father I:1 D: who carries the mutation heterozygously. The ages at the time of investigation of individuals II:4, II:6, and II:7 were 36, 28, and 26, respectively. Fundus examination of the affected individuals revealed typical features of retinitis pigmentosa, bone spicule-like pigmentations were found in the mid periphery of retina (indicated with arrows), and retinal vessels were attenuated (arrowheads).
Mentions: All three affected individuals (II:4, II:6, and II:7) presented with night blindness that started at an early age. They displayed gradual constriction of their visual field and low visual acuity. Fundus examination revealed typical RP including the bone spicule-like pigment deposits in the mid-peripheral retina and narrowing of the retinal vessels (Figure 2). The unaffected sibling (II:2) did not experience night blindness or any other symptoms of RP. Apart from slightly decreased visual acuity, which is probably age-related, the proband's father (I:1) did not display any ophthalmological symptoms either. The clinical data for all participating individuals are summarized in Table 2.

Bottom Line: Unaffected family members either carried two wild-type alleles or were heterozygous carriers of the mutation.Most of the previously reported RP1 mutations are inherited in an autosomal dominant mode, and appear to cluster in exon 4.Here, we identified a novel homozygous p.R338* mutation in exon 4 of RP1, and speculate on the mutational mechanisms of different RP1 mutations underlying dominant and recessive RP.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

ABSTRACT

Purpose: The purpose of this study was to identify the underlying molecular genetic defect in an Indonesian family with three affected individuals who had received a diagnosis of retinitis pigmentosa (RP).

Methods: Clinical evaluation of the family members included measuring visual acuity and fundoscopy, and assessing visual field and color vision. Genomic DNA of the three affected individuals was analyzed with Illumina 700k single nucleotide polymorphism (SNP) arrays, and homozygous regions were identified using PLINK software. Mutation analysis was performed with sequence analysis of the retinitis pigmentosa 1 (RP1) gene that resided in one of the homozygous regions. The frequency of the identified mutation in the Indonesian population was determined with TaqI restriction fragment length polymorphism analysis.

Results: A novel homozygous nonsense mutation in exon 4 of the RP1 gene, c.1012C>T (p.R338*), was identified in the proband and her two affected sisters. Unaffected family members either carried two wild-type alleles or were heterozygous carriers of the mutation. The mutation was not present in 184 Indonesian control samples.

Conclusions: Most of the previously reported RP1 mutations are inherited in an autosomal dominant mode, and appear to cluster in exon 4. Here, we identified a novel homozygous p.R338* mutation in exon 4 of RP1, and speculate on the mutational mechanisms of different RP1 mutations underlying dominant and recessive RP.

Show MeSH
Related in: MedlinePlus