A new locus (RP31) for autosomal dominant retinitis pigmentosa maps to chromosome 9p

Papaioannou, Myrto; Chakarova, Christina; Prescott, Quincy; Waseem, Naushin; Theis, Thorsten; López, Irma; Gill, Bhavdip; Koenekoop, Robert K.; Bhattacharya, Siladitya

doi:10.1007/s00439-005-0063-3

Cited by 11 publications

(8 citation statements)

References 4 publications

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“…RP33 thus represents a genetically distinct form of adRP and is the first adRP locus assigned to chromosome 2. Taken together with previous reports, and the recent identification of RP31 in 9q (Papaioannou et al 2005), the present study brings the total number of known adRP loci to 17. While the disease genes for 15 of these loci have been identified, RP31 and RP33 remain to be identified by positional cloning.…”

Section: Discussionsupporting

confidence: 61%

A novel locus (RP33) for autosomal dominant retinitis pigmentosa mapping to chromosomal region 2cen-q12.1

Zhao

Zhou

et al. 2006

Hum Genet

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Retinitis pigmentosa (RP) is a heterogeneous group of progressive degenerative disorders of the retina with a strong genetic component. Here, we report the clinical and genetic findings in a Chinese family in which autosomal dominant RP (adRP) was inherited by 13 affected members in four generations. Using a genome-wide linkage screening approach, a novel disease locus (RP33) was assigned to the long arm of chromosome 2. A maximum multi-point LOD score of 4.69 was reached at marker D2S2222 in 2q11.2. Meiotic recombination events in affected members placed RP33 in a 15.5 cM region between D2S329 and D2S2229. From meiotic recombinations in two unaffected members RP33 was further refined to a 4.8 cM (9.5 Mb) interval flanked by D2S2159 and D2S1343 in chromosomal region 2cen-q12.1. No disease-associated mutations were detected in the candidate genes SEMA4C, CNGA3 or HNK1ST from within the region. MERTK, a known disease gene for autosomal recessive RP located close to RP33 was similarly excluded. Clinically, the family presented relatively late onset of night blindness, gradually decreased visual acuity, progressive loss of peripheral visual field and typical RP fundus changes in the mid-periphery of the retina. In conclusion, a novel locus for adRP has been assigned to chromosomal region 2cen-q12.1, which in the present kindred was associated with a relatively late onset form of the disease.

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Section: Discussionsupporting

confidence: 61%

A novel locus (RP33) for autosomal dominant retinitis pigmentosa mapping to chromosomal region 2cen-q12.1

Zhao

Zhou

et al. 2006

Hum Genet

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“…30 Several studies have identified mutations in the TOPORS gene that cause dominant RP. 31,32 TOPORS is a cilia-centrosomal protein that localizes to the basal bodies of connecting cilium and to the centrosomes of cultured cells. Morpholino-mediated silencing of topors in zebrafish embryos demonstrated defective retinal development and failure to form outer segments.…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing Identifies CRB1 Defect in an Unusual Maculopathy Phenotype

Tsang¹,

Burke²,

Oll³

et al. 2014

Ophthalmology

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Objective To report a new phenotype caused by mutations in the CRB1 gene in a family with 2 affected siblings. Design Molecular genetics and observational case studies. Participants Two affected siblings and 3 unaffected family members. Methods Each subject received a complete ophthalmic examination together with color fundus photography, fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT). Microperimetry 1 (MP-1) mapping and electroretinogram (ERG) analysis were performed on the proband. Screening for disease-causing mutations was performed by whole exome sequencing in 3 family members followed by segregation analyses in the entire family. Main Outcome Measures Appearance of the macula as examined by clinical examination, fundus photography, FAF imaging, SD-OCT, and visual function by MP-1 and ERG. Results The proband and her affected brother exhibited unusual, previously unreported, findings of a macular dystrophy with relative sparing of the retinal periphery beyond the vascular arcades. The FAF imaging showed severely affected areas of hypoautofluorescence that extended nasally beyond the optic disc in both eyes. A central macular patch of retinal pigment epithelium (RPE) sparing was evident in both eyes on FAF, whereas photoreceptor sparing was documented in the right eye only using SD-OCT. The affected brother presented with irregular patterns of autofluorescence in both eyes characterized by concentric rings of alternating hyper- and hypoautofluorescence, and foveal sparing of photoreceptors and RPE, as seen on SD-OCT, bilaterally. After negative results in screening for mutations in candidate genes including ABCA4 and PRPH2, DNA from 3 members of the family, including both affected siblings and their mother, was screened by whole exome sequencing resulting in identification of 2 CRB1 missense mutations, c.C3991T:p.R1331C and c.C4142T:p.P1381L, which segregated with the disease in the family. Of the 2, the p.R1331C CRB1 mutation has not been described before and the p.P1381L variant has been described in 1 patient with Leber congenital amaurosis. Conclusions This report illustrates a novel presentation of a macular dystrophy caused by CRB1 mutations. Both affected siblings exhibited a relatively well-developed retinal structure and preservation of generalized retinal function. An unusual 5-year progression of macular atrophy alone was observed that has not been described in any other CRB1-associated phenotypes.

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“…58 Linkage mapping continues to locate new adRP genes-most recently RP31 and RP33. 59,60 Likewise, new recessive and X-linked genes are reported regularly. 1 It is impossible to predict whether there are several or many more RP genes that have yet to be discov-ered.…”

Section: Genes and Mutations Causing Adrpmentioning

confidence: 95%

Perspective on Genes and Mutations Causing Retinitis Pigmentosa

2007

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A new locus (RP31) for autosomal dominant retinitis pigmentosa maps to chromosome 9p

Cited by 11 publications

References 4 publications

A novel locus (RP33) for autosomal dominant retinitis pigmentosa mapping to chromosomal region 2cen-q12.1

A novel locus (RP33) for autosomal dominant retinitis pigmentosa mapping to chromosomal region 2cen-q12.1

Whole Exome Sequencing Identifies CRB1 Defect in an Unusual Maculopathy Phenotype

Perspective on Genes and Mutations Causing Retinitis Pigmentosa

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