Characterization of Macular Structure and Function in Two Swedish Families with Genetically Identified Autosomal Dominant Retinitis Pigmentosa

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2016 May 24

PMID 27212874

Citations 6

Authors

Wissam Abdulridha-Aboud

Ulrika Kjellstrom

Sten Andreasson

Vesna Ponjavic

Affiliations

Soon will be listed here.

Abstract

Purpose: To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function.

Methods: Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP.

Results: The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG.

Conclusions: These two families demonstrate the extreme inter- and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype.

Citing Articles

Clinical Evidence for the Importance of the Wild-Type Allele in the Phenotypic Expression of RP11.

Roshandel D, Thompson J, Heath Jeffery R, Zhang D, Lamey T, McLaren T Genes (Basel). 2021; 12(6).

PMID: 34198599 PMC: 8232116. DOI: 10.3390/genes12060915.

Retinal Dystrophies and the Road to Treatment: Clinical Requirements and Considerations.

Talib M, Boon C Asia Pac J Ophthalmol (Phila). 2020; 9(3):159-179.

PMID: 32511120 PMC: 7299224. DOI: 10.1097/APO.0000000000000290.

Mutation spectrum of PRPF31, genotype-phenotype correlation in retinitis pigmentosa, and opportunities for therapy.

Wheway G, Douglas A, Baralle D, Guillot E Exp Eye Res. 2020; 192:107950.

PMID: 32014492 PMC: 7065041. DOI: 10.1016/j.exer.2020.107950.

Heterozygous p.R135W missense mutation in a large Han-Chinese family with retinitis pigmentosa and different refractive errors.

Wu Y, Guo Y, Yi J, Xu H, Yuan L, Yang Z Biosci Rep. 2019; 39(7).

PMID: 31239368 PMC: 6629948. DOI: 10.1042/BSR20182198.

Identification of a novel pathogenic missense mutation in using whole exome sequencing: a case report.

Bryant L, Lozynska O, Marsh A, Papp T, Van Gorder L, Serrano L Br J Ophthalmol. 2018; 103(6):761-767.

PMID: 30030392 PMC: 6582727. DOI: 10.1136/bjophthalmol-2017-311405.

References

Hood D, Bach M, Brigell M, Keating D, Kondo M, Lyons J . ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol. 2011; 124(1):1-13. PMC: 4466109. DOI: 10.1007/s10633-011-9296-8. View

Golovleva I, Kohn L, Burstedt M, Daiger S, Sandgren O . Mutation spectra in autosomal dominant and recessive retinitis pigmentosa in northern Sweden. Adv Exp Med Biol. 2010; 664:255-62. PMC: 4113316. DOI: 10.1007/978-1-4419-1399-9_29. View

Rose A, Shah A, Venturini G, Rivolta C, Rose G, Bhattacharya S . Dominant PRPF31 mutations are hypostatic to a recessive CNOT3 polymorphism in retinitis pigmentosa: a novel phenomenon of "linked trans-acting epistasis". Ann Hum Genet. 2013; 78(1):62-71. PMC: 4240469. DOI: 10.1111/ahg.12042. View

Xiao X, Guo X, Jia X, Li S, Wang P, Zhang Q . A recurrent mutation in GUCY2D associated with autosomal dominant cone dystrophy in a Chinese family. Mol Vis. 2011; 17:3271-8. PMC: 3244478. View

Walia S, Fishman G, Jacobson S, Aleman T, Koenekoop R, Traboulsi E . Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosa. Ophthalmology. 2010; 117(6):1190-8. DOI: 10.1016/j.ophtha.2009.09.056. View

Ponjavic V, Abrahamson M, Andreasson S, Ehinger B, Fex G . Autosomal dominant retinitis pigmentosa with a rhodopsin mutation (Arg-135-Trp). Disease phenotype in a Swedish family. Acta Ophthalmol Scand. 1997; 75(2):218-23. DOI: 10.1111/j.1600-0420.1997.tb00129.x. View

Utz V, Beight C, Marino M, Hagstrom S, Traboulsi E . Autosomal dominant retinitis pigmentosa secondary to pre-mRNA splicing-factor gene PRPF31 (RP11): review of disease mechanism and report of a family with a novel 3-base pair insertion. Ophthalmic Genet. 2013; 34(4):183-8. DOI: 10.3109/13816810.2012.762932. View

Audo I, Manes G, Mohand-Said S, Friedrich A, Lancelot M, Antonio A . Spectrum of rhodopsin mutations in French autosomal dominant rod-cone dystrophy patients. Invest Ophthalmol Vis Sci. 2010; 51(7):3687-700. PMC: 3102265. DOI: 10.1167/iovs.09-4766. View

Small K, Silva-Garcia R, Udar N, Nguyen E, Heckenlively J . New mutation, P575L, in the GUCY2D gene in a family with autosomal dominant progressive cone degeneration. Arch Ophthalmol. 2008; 126(3):397-403. DOI: 10.1001/archopht.126.3.397. View

10.

Andreasson S, Ehinger B, Abrahamson M, Fex G . A six-generation family with autosomal dominant retinitis pigmentosa and a rhodopsin gene mutation (arginine-135-leucine). Ophthalmic Paediatr Genet. 1992; 13(3):145-53. DOI: 10.3109/13816819209046483. View

11.

Kitiratschky V, Wilke R, Renner A, Kellner U, Vadala M, Birch D . Mutation analysis identifies GUCY2D as the major gene responsible for autosomal dominant progressive cone degeneration. Invest Ophthalmol Vis Sci. 2008; 49(11):5015-23. PMC: 5358799. DOI: 10.1167/iovs.08-1901. View

12.

Kohn L, Bowne S, Sullivan L, Daiger S, Burstedt M, Kadzhaev K . Breakpoint characterization of a novel approximately 59 kb genomic deletion on 19q13.42 in autosomal-dominant retinitis pigmentosa with incomplete penetrance. Eur J Hum Genet. 2008; 17(5):651-5. PMC: 2796252. DOI: 10.1038/ejhg.2008.223. View

13.

Holm K, Larsson J, Lovestam-Adrian M . In diabetic retinopathy, foveal thickness of 300 mum seems to correlate with functionally significant loss of vision. Doc Ophthalmol. 2007; 114(3):117-24. DOI: 10.1007/s10633-006-9044-7. View

14.

Jin Z, Gu F, Matsuda H, Yukawa N, Ma X, Nao-I N . Somatic and gonadal mosaicism in X-linked retinitis pigmentosa. Am J Med Genet A. 2007; 143A(21):2544-8. DOI: 10.1002/ajmg.a.31984. View

15.

Marmor M, Fulton A, Holder G, Miyake Y, Brigell M, Bach M . ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol. 2008; 118(1):69-77. DOI: 10.1007/s10633-008-9155-4. View

16.

Yoon C, Yu H . The Structure-Function Relationship between Macular Morphology and Visual Function Analyzed by Optical Coherence Tomography in Retinitis Pigmentosa. J Ophthalmol. 2013; 2013:821460. PMC: 3866715. DOI: 10.1155/2013/821460. View

17.

Kjellstrom U . Association between genotype and phenotype in families with mutations in the ABCA4 gene. Mol Vis. 2014; 20:89-104. PMC: 3892680. View

18.

Oh K, Oh D, Weleber R, Stone E, Parikh A, White J . Genotype-phenotype correlation in a family with Arg135Leu rhodopsin retinitis pigmentosa. Br J Ophthalmol. 2004; 88(12):1533-7. PMC: 1772449. DOI: 10.1136/bjo.2004.043653. View

19.

Raas-Rothschild A, Wanders R, Mooijer P, Gootjes J, Waterham H, Gutman A . A PEX6-defective peroxisomal biogenesis disorder with severe phenotype in an infant, versus mild phenotype resembling Usher syndrome in the affected parents. Am J Hum Genet. 2002; 70(4):1062-8. PMC: 379104. DOI: 10.1086/339766. View

20.

Villanueva A, Willer J, Bryois J, Dermitzakis E, Katsanis N, Davis E . Whole exome sequencing of a dominant retinitis pigmentosa family identifies a novel deletion in PRPF31. Invest Ophthalmol Vis Sci. 2014; 55(4):2121-9. PMC: 3979517. DOI: 10.1167/iovs.13-13827. View