Macular Dystrophies Associated with Stargardt-like Phenotypes

Overview

Journal Arq Bras Oftalmol

Specialty Ophthalmology

Date 2023 Mar 30

PMID 36995812

Authors

Rebeca A S Amaral

Olivia A Zin

Mariana V Salles

Fabiana L Motta

Juliana Maria Ferraz Sallum

Affiliations

Soon will be listed here.

Abstract

Purpose: Stargardt-like phenotype has been described as associated with pathogenic variants besides the ABCA4 gene. This study aimed to describe four cases with retinal appearance of Stargardt disease phenotypes and unexpected molecular findings.

Methods: This report reviewed medical records of four patients with macular dystrophy and clinical features of Stargardt disease. Ophthalmic examination, fundus imaging, and next-generation sequencing were performed to evaluate pathogenic variants related to the phenotypes.

Results: Patients presented macular atrophy and pigmentary changes suggesting Stargardt disease. The phenotypes of the two patients were associated with autosomal dominant inheritance pattern genes (RIMS1 and CRX) and in the other two patients were associated with recessive dominant inheritance pattern genes (CRB1 and RDH12) with variants predicted to be pathogenic.

Conclusion: Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones.

Citing Articles

How to Set Up Genetic Counselling for Inherited Macular Dystrophies: Focus on Genetic Characterization.

Raimondi R, DEsposito F, Sorrentino T, Tsoutsanis P, De Rosa F, Stradiotto E Int J Mol Sci. 2023; 24(11).

PMID: 37298674 PMC: 10253412. DOI: 10.3390/ijms24119722.

References

Michaelides M, Hunt D, Moore A . The genetics of inherited macular dystrophies. J Med Genet. 2003; 40(9):641-50. PMC: 1735576. DOI: 10.1136/jmg.40.9.641. View

Lotery A, Jacobson S, Fishman G, Weleber R, Fulton A, Namperumalsamy P . Mutations in the CRB1 gene cause Leber congenital amaurosis. Arch Ophthalmol. 2001; 119(3):415-20. DOI: 10.1001/archopht.119.3.415. View

Armstrong J, Meyer D, Xu S, Elfervig J . Long-term follow-up of Stargardt's disease and fundus flavimaculatus. Ophthalmology. 1998; 105(3):448-57; discussion 457-8. DOI: 10.1016/S0161-6420(98)93026-3. View

Kong X, Fujinami K, Strauss R, Munoz B, West S, Cideciyan A . Visual Acuity Change Over 24 Months and Its Association With Foveal Phenotype and Genotype in Individuals With Stargardt Disease: ProgStar Study Report No. 10. JAMA Ophthalmol. 2018; 136(8):920-928. PMC: 6142940. DOI: 10.1001/jamaophthalmol.2018.2198. View

Swain P, Chen S, Wang Q, Affatigato L, Coats C, Brady K . Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration. Neuron. 1998; 19(6):1329-36. DOI: 10.1016/s0896-6273(00)80423-7. View

Riveiro-Alvarez R, Vallespin E, Wilke R, Garcia-Sandoval B, Cantalapiedra D, Aguirre-Lamban J . Molecular analysis of ABCA4 and CRB1 genes in a Spanish family segregating both Stargardt disease and autosomal recessive retinitis pigmentosa. Mol Vis. 2008; 14:262-7. PMC: 2258218. View

Khan K, Robson A, Mahroo O, Arno G, Inglehearn C, Armengol M . A clinical and molecular characterisation of CRB1-associated maculopathy. Eur J Hum Genet. 2018; 26(5):687-694. PMC: 5945653. DOI: 10.1038/s41431-017-0082-2. View

Westeneng-Van Haaften S, Boon C, Cremers F, Hoefsloot L, den Hollander A, Hoyng C . Clinical and genetic characteristics of late-onset Stargardt's disease. Ophthalmology. 2012; 119(6):1199-210. DOI: 10.1016/j.ophtha.2012.01.005. View

Tanna P, Strauss R, Fujinami K, Michaelides M . Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options. Br J Ophthalmol. 2016; 101(1):25-30. PMC: 5256119. DOI: 10.1136/bjophthalmol-2016-308823. View

10.

Donoso L, Edwards A, Frost A, Vrabec T, Stone E, Hageman G . Autosomal dominant Stargardt-like macular dystrophy. Surv Ophthalmol. 2001; 46(2):149-63. DOI: 10.1016/s0039-6257(01)00251-x. View

11.

Fingert J, Oh K, Chung M, Scheetz T, Andorf J, Johnson R . Association of a novel mutation in the retinol dehydrogenase 12 (RDH12) gene with autosomal dominant retinitis pigmentosa. Arch Ophthalmol. 2008; 126(9):1301-7. DOI: 10.1001/archopht.126.9.1301. View

12.

Aleman T, Uyhazi K, Serrano L, Vasireddy V, Bowman S, Ammar M . RDH12 Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function. Invest Ophthalmol Vis Sci. 2018; 59(12):5225-5236. DOI: 10.1167/iovs.18-24708. View

13.

Jacobson S, Cideciyan A, Aleman T, Pianta M, Sumaroka A, Schwartz S . Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Hum Mol Genet. 2003; 12(9):1073-8. DOI: 10.1093/hmg/ddg117. View

14.

Hull S, Arno G, Plagnol V, Chamney S, Russell-Eggitt I, Thompson D . The phenotypic variability of retinal dystrophies associated with mutations in CRX, with report of a novel macular dystrophy phenotype. Invest Ophthalmol Vis Sci. 2014; 55(10):6934-44. DOI: 10.1167/iovs.14-14715. View

15.

Cremers F, van de Pol D, van Driel M, den Hollander A, van Haren F, Knoers N . Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR. Hum Mol Genet. 1998; 7(3):355-62. DOI: 10.1093/hmg/7.3.355. View

16.

Perrault I, Hanein S, Gerber S, Barbet F, Ducroq D, Dollfus H . Retinal dehydrogenase 12 (RDH12) mutations in leber congenital amaurosis. Am J Hum Genet. 2004; 75(4):639-46. PMC: 1182050. DOI: 10.1086/424889. View

17.

Kniazeva M, Chiang M, Cutting G, Zack D, Han M, Zhang K . Clinical and genetic studies of an autosomal dominant cone-rod dystrophy with features of Stargardt disease. Ophthalmic Genet. 1999; 20(2):71-81. DOI: 10.1076/opge.20.2.71.2287. View

18.

Maeda A, Golczak M, Maeda T, Palczewski K . Limited roles of Rdh8, Rdh12, and Abca4 in all-trans-retinal clearance in mouse retina. Invest Ophthalmol Vis Sci. 2009; 50(11):5435-43. PMC: 2792889. DOI: 10.1167/iovs.09-3944. View

19.

Nishiguchi K, Kunikata H, Fujita K, Hashimoto K, Koyanagi Y, Akiyama M . Association of CRX genotypes and retinal phenotypes confounded by variable expressivity and electronegative electroretinogram. Clin Exp Ophthalmol. 2020; 48(5):644-657. DOI: 10.1111/ceo.13743. View

20.

Freund C, Gregory-Evans C, Furukawa T, Papaioannou M, Looser J, Ploder L . Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Cell. 1997; 91(4):543-53. DOI: 10.1016/s0092-8674(00)80440-7. View