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A novel crumbs homolog 1 mutation in a family with retinitis pigmentosa, nanophthalmos, and optic disc drusen.

Paun CC, Pijl BJ, Siemiatkowska AM, Collin RW, Cremers FP, Hoyng CB, den Hollander AI - Mol. Vis. (2012)

Bottom Line: After MFRP was excluded, genome-wide homozygosity mapping was performed with 250 K single nucleotide polymorphism (SNP) microarrays.Ophthalmological evaluation of both affected individuals in the family revealed a decreased axial length (18-19 mm), retinal dystrophy, macular edema, and hyperopia of >+8.0 diopters.In this study, we demonstrated that a similar disease complex can be caused by mutations in the CRB1 gene.

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 is to identify the genetic defect in a Turkish family with autosomal recessive retinitis pigmentosa, nanophthalmos, and optic disc drusen.

Methods: Ophthalmological examinations consisted of measuring the best-corrected visual acuity and the refractive error, electroretinography, optical coherence tomography, B-mode ultrasonography, and fundus photography. The involvement of the membrane frizzled-related protein (MFRP) gene in this family was studied with direct DNA sequencing of the coding exons of MFRP and with linkage analysis with microsatellite markers. After MFRP was excluded, genome-wide homozygosity mapping was performed with 250 K single nucleotide polymorphism (SNP) microarrays. Mutation analysis of the crumbs homolog 1 (CRB1) gene was performed with direct sequencing.

Results: Ophthalmological evaluation of both affected individuals in the family revealed a decreased axial length (18-19 mm), retinal dystrophy, macular edema, and hyperopia of >+8.0 diopters. Sequencing of MFRP did not reveal any pathogenic changes, and microsatellite marker analysis showed that the chromosomal region did not segregate within the disease in this family. Genome-wide homozygosity mapping using single nucleotide polymorphism microarrays revealed a 28-Mb homozygous region encompassing the CRB1 gene, and direct sequencing disclosed a novel homozygous missense mutation (p.Gly833Asp) in CRB1.

Conclusions: Previous studies associated mutations in the MFRP gene with the syndrome nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen. In this study, we demonstrated that a similar disease complex can be caused by mutations in the CRB1 gene.

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Related in: MedlinePlus

Ophthalmological images of two siblings affected by retinitis pigmentosa, nanophthalmus and optic disc drusen. Fundus photography of the right eye of patient IV:2 A: and of patient IV:3 B: showed atrophy of the retina outside the fovea and spots of hyperpigmentation. B-mode ultrasound of the left eye of patient IV:2 C: revealed optic disc drusen (indicated with the yellow arrow). Optical coherence tomography scan of the macula of patient IV:2 showed intraretinal edema and atrophy of the outer retinal layers D.
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f1: Ophthalmological images of two siblings affected by retinitis pigmentosa, nanophthalmus and optic disc drusen. Fundus photography of the right eye of patient IV:2 A: and of patient IV:3 B: showed atrophy of the retina outside the fovea and spots of hyperpigmentation. B-mode ultrasound of the left eye of patient IV:2 C: revealed optic disc drusen (indicated with the yellow arrow). Optical coherence tomography scan of the macula of patient IV:2 showed intraretinal edema and atrophy of the outer retinal layers D.

Mentions: Table 3 summarizes the ophthalmologic features of both affected individuals. Both patients demonstrated bilateral decreased axial length, retinal dystrophy, and macular edema (Figure 1). Patient IV:2 had optic disc drusen on funduscopy and confirmed by B-mode ultrasound, whereas patient IV:3 did not have optic disc drusen. The ERG for patient IV:3 showed an extinguished rod response and a subnormal cone photopic response. In patient IV:2, the rod and cone responses were extinguished on the ERG.


A novel crumbs homolog 1 mutation in a family with retinitis pigmentosa, nanophthalmos, and optic disc drusen.

Paun CC, Pijl BJ, Siemiatkowska AM, Collin RW, Cremers FP, Hoyng CB, den Hollander AI - Mol. Vis. (2012)

Ophthalmological images of two siblings affected by retinitis pigmentosa, nanophthalmus and optic disc drusen. Fundus photography of the right eye of patient IV:2 A: and of patient IV:3 B: showed atrophy of the retina outside the fovea and spots of hyperpigmentation. B-mode ultrasound of the left eye of patient IV:2 C: revealed optic disc drusen (indicated with the yellow arrow). Optical coherence tomography scan of the macula of patient IV:2 showed intraretinal edema and atrophy of the outer retinal layers D.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472923&req=5

f1: Ophthalmological images of two siblings affected by retinitis pigmentosa, nanophthalmus and optic disc drusen. Fundus photography of the right eye of patient IV:2 A: and of patient IV:3 B: showed atrophy of the retina outside the fovea and spots of hyperpigmentation. B-mode ultrasound of the left eye of patient IV:2 C: revealed optic disc drusen (indicated with the yellow arrow). Optical coherence tomography scan of the macula of patient IV:2 showed intraretinal edema and atrophy of the outer retinal layers D.
Mentions: Table 3 summarizes the ophthalmologic features of both affected individuals. Both patients demonstrated bilateral decreased axial length, retinal dystrophy, and macular edema (Figure 1). Patient IV:2 had optic disc drusen on funduscopy and confirmed by B-mode ultrasound, whereas patient IV:3 did not have optic disc drusen. The ERG for patient IV:3 showed an extinguished rod response and a subnormal cone photopic response. In patient IV:2, the rod and cone responses were extinguished on the ERG.

Bottom Line: After MFRP was excluded, genome-wide homozygosity mapping was performed with 250 K single nucleotide polymorphism (SNP) microarrays.Ophthalmological evaluation of both affected individuals in the family revealed a decreased axial length (18-19 mm), retinal dystrophy, macular edema, and hyperopia of >+8.0 diopters.In this study, we demonstrated that a similar disease complex can be caused by mutations in the CRB1 gene.

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 is to identify the genetic defect in a Turkish family with autosomal recessive retinitis pigmentosa, nanophthalmos, and optic disc drusen.

Methods: Ophthalmological examinations consisted of measuring the best-corrected visual acuity and the refractive error, electroretinography, optical coherence tomography, B-mode ultrasonography, and fundus photography. The involvement of the membrane frizzled-related protein (MFRP) gene in this family was studied with direct DNA sequencing of the coding exons of MFRP and with linkage analysis with microsatellite markers. After MFRP was excluded, genome-wide homozygosity mapping was performed with 250 K single nucleotide polymorphism (SNP) microarrays. Mutation analysis of the crumbs homolog 1 (CRB1) gene was performed with direct sequencing.

Results: Ophthalmological evaluation of both affected individuals in the family revealed a decreased axial length (18-19 mm), retinal dystrophy, macular edema, and hyperopia of >+8.0 diopters. Sequencing of MFRP did not reveal any pathogenic changes, and microsatellite marker analysis showed that the chromosomal region did not segregate within the disease in this family. Genome-wide homozygosity mapping using single nucleotide polymorphism microarrays revealed a 28-Mb homozygous region encompassing the CRB1 gene, and direct sequencing disclosed a novel homozygous missense mutation (p.Gly833Asp) in CRB1.

Conclusions: Previous studies associated mutations in the MFRP gene with the syndrome nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen. In this study, we demonstrated that a similar disease complex can be caused by mutations in the CRB1 gene.

Show MeSH
Related in: MedlinePlus