Molecular genetic diagnosis of Stargardt disease

N.L. Sheremet

FGBU "NII glaznykh bolezneĭ" RAMN

N.V. Zhorzholadze

FGBU "NII glaznykh bolezneĭ" RAMN

I.A. Ronzina

FGBU "NII glaznykh bolezneĭ" RAMN, Moskva

I.G. Grushke

Research Institute of Eye Diseases, 11 A, B, Rossolimo St., Moscow, Russia, 119021

S.A. Kurbatov

Regional non-governmental organization «Society of neuro-muscular diseases specialists», Moscow

A.L. Chukhrova

FGBU "Mediko-geneticheskiĭ nauchnyĭ tsentr" RAMN, Moskva

A.N. Loginova

FGBU "Mediko-geneticheskiĭ nauchnyĭ tsentr" RAMN, Moskva

P.O. Shcherbakova

Pirogov Russian National Research Medical University, 1 Ostrovityanova St., Moscow, Russia, 117997

A.S. Tanas

Research Centre of Medical Genetics, 1 Moskvorech’e St., Moscow, Russia, 115478

A.V. Poliakov

Mediko-geneticheskiĭ nauchnyĭ tsentr RAMN, Moskva

V.V. Strel’nikov

Research Centre of Medical Genetics, 1 Moskvorech’e St., Moscow, Russian Federation, 115478

Molecular genetic diagnosis of Stargardt disease

Authors:

N.L. Sheremet, N.V. Zhorzholadze, I.A. Ronzina, I.G. Grushke, S.A. Kurbatov, A.L. Chukhrova, A.N. Loginova, P.O. Shcherbakova, A.S. Tanas, A.V. Poliakov, V.V. Strel’nikov

More about the authors

Journal: Russian Annals of Ophthalmology. 2017;133(4): 4‑11

DOI: 10.17116/oftalma201713344-11

Downloaded: 19

To cite this article:

Sheremet NL, Zhorzholadze NV, Ronzina IA, Grushke IG, Kurbatov SA, Chukhrova AL, Loginova AN, Shcherbakova PO, Tanas AS, Poliakov AV, Strel’nikov VV. Molecular genetic diagnosis of Stargardt disease. Russian Annals of Ophthalmology. 2017;133(4):4‑11. (In Russ., In Engl.)
https://doi.org/10.17116/oftalma201713344-11

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Aim — to comparatively evaluate the efficacy of genetic screening in patients with Stargardt disease (SD) by using an express panel of 5 most common ABCA4 mutations and performing massive parallel sequencing of all coding regions of the ABCA4, ELOVL4, PROM1, and CNGB3 genes. Material and methods. MLPA analysis for 5 ABCA4 mutations, namely p.G863A, p.L541P, p.A1038V, p.G1961E, and p.P1380L, was done in 54 patients with SD. In 25 patients, massive parallel sequencing of coding regions (exons) and neighboring introns of the ABCA4, ELOVL4, PROM1, and CNGB3 genes was also performed. Results. Gene testing for 5 ABCA4 mutations showed that 50% of patients (27 patients) harbored one mutation and 13% - two mutations. At massive parallel sequencing (25 patients), two pathogenic alleles were found in 21 patients (84%), one mutation — in 23 patients (91.7%). The majority of mutations was accounted for by the ABCA4 gene (83% of all mutation-positive patients). Conclusion. Sequencing of exons and neighboring introns of the ABCA4, ELOVL4, PROM1, and CNGB3 genes with the new molecular genetic diagnostic system enabled confirmation of the diagnosis of SD in 84% of patients. High prevalence of p.L541P, p.A1038V, and p.G1961E mutations of the ABCA4 gene has been established.

Keywords:

Stargardt disease

mutation

ABCA4

ELOVL4

PROM1

CNGB3

massive parallel sequencing

genetic panel

next-generation sequencing

Authors:

N.L. Sheremet

FGBU "NII glaznykh bolezneĭ" RAMN

N.V. Zhorzholadze

FGBU "NII glaznykh bolezneĭ" RAMN

I.A. Ronzina

FGBU "NII glaznykh bolezneĭ" RAMN, Moskva

I.G. Grushke

Research Institute of Eye Diseases, 11 A, B, Rossolimo St., Moscow, Russia, 119021

S.A. Kurbatov

Regional non-governmental organization «Society of neuro-muscular diseases specialists», Moscow

A.L. Chukhrova

FGBU "Mediko-geneticheskiĭ nauchnyĭ tsentr" RAMN, Moskva

A.N. Loginova

FGBU "Mediko-geneticheskiĭ nauchnyĭ tsentr" RAMN, Moskva

P.O. Shcherbakova

Pirogov Russian National Research Medical University, 1 Ostrovityanova St., Moscow, Russia, 117997

A.S. Tanas

Research Centre of Medical Genetics, 1 Moskvorech’e St., Moscow, Russia, 115478

A.V. Poliakov

Mediko-geneticheskiĭ nauchnyĭ tsentr RAMN, Moskva

V.V. Strel’nikov

Research Centre of Medical Genetics, 1 Moskvorech’e St., Moscow, Russian Federation, 115478

List of references:

Simonelli F, Testa F, de Crecchio G, Rinaldi E, Hutchinson A, Atkinson A, Dean M, D’Urso M, Allikmets R. New ABCR mutations and clinical phenotype in Italian patients with Stargardt disease. Invest Ophthalmol Vis Sci. 2000;41(3):892-897.
Hargitai J, Zernant J, Gabor M Somfai, Rita Vamos Agnes Farkas, Salacz G, Allikmets R. Correlation of Clinical and Genetic Findings in Hungarian Patients with Stargardt Disease. Investigative Ophthalmology & Visual Science. 2005;46:12. https://doi.org/10.1167/iovs.05-0504
http://www.hgmd.cf.ac.uk/ac/index.php
http://www.vision2020.org/
Hwang JC, Zernant J, Allikmets R, Barile GR, Chang S, Smith RT. Peripapillary atrophy in Stargardt disease. Retina. 2009;29(2):181-186. https://doi.org/10.1097/IAE.0b013e31818a2c01
Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, Martin C, Meloche C, Gravel M, Drouin C A, Rouleau G A, Nguyen D K, Cossette P. Expanding the clinical phenotype associated with ELOVL4 mutation:study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. JAMA Neurol. 2014;71:470-475. https://doi.org/10.1001/jamaneurol.2013.6337
Chacón-Camacho OF, Granillo-Alvarez M, Ayala-Ramírez R, Zenteno JC. ABCA4 mutational spectrum in Mexican patients with Stargardt disease: Identification of 12 novel mutations and evidence of a founder effect for the common p.A1773V mutation. Exp Eye Res. 2013;109:77-82. https://doi.org/10.1016/j.exer.2013.02.006
Berisha F, Feke G T, Aliyeva S, Hirai K, Pfeiffer N,Hirose T. Evaluation of macular abnormalities in Stargardt’s disease using optical coherence tomography and scanning laser ophthalmoscope microperimetry. Graefes Arch Clin Exp Ophthalmol. 2009;247(3):303-309. https://doi.org/10.1007/s00417-008-0963-8
Kniazeva M, Chiang M F, Morgan B, Anduz, A L, Zack D J, Han M, Zhang K. A new locus for autosomal dominant Stargardt-like disease maps to chromosome 4. Am J Hum Genet. 1999;64:1394-1399.
Noble KG, Carr RE. Stargardt’s disease and fundus flavimaculatus. Arch Ophthalmol. 1979;97(7):1281-1285.
Sheremet NL, Ronzina IA Zhorzholadze NV, Strelnikov VV. Correlation of structural and functional changes in the retina with Stargardt’s disease. Vestnik oftal’mologii. 2016;132(3):42-48. (In Russ.) https://doi.org/10.17116/oftalma2016132342-48
Braun TA, Mullins RF, Wagner AH, Andorf JL, Johnston RM, Bakall BB, Deluca AP, Fishman GA, Lam BL, Weleber RG et al. Non-exomic and synonymous variants in ABCA4 are an important cause of Stargardt disease. Hum Mol Genet. 2013;22:5136-5145. https://doi.org/10.1093/hmg/ddt367
Burke TR, Tsang SH, Zernant J, Smith RT, Allikmets R. Familial discordance in Stargardt disease. Molecular Vision. 2012;18:227-233.
Karandasheva KO, Zhorzholadze NV, Sheremet NL, Kuznetsov EB, Thanas AS, Anoshkin KI, Zaletaev DV, Strelnikov VV. Cryptic splice site mutations in the non-coding regions of the ABCA4 gene in Stargardt disease patients. Medicinskaja genetika. 2016;6:31-36. (In Russ.)
Shurygina MF, Borzenok SA, Hlebnikova OV, Solomin VA. Clinical and molecular genetic characteristics of central hereditary retinal disease in Russian Federetion. Vestnik OGU. 2013;4(153):311-314. (In Russ.)
Michaelides M, Gaillard MC, Escher P, Tiab L, Bedell M, Borruat FX, Barthelmes D, Carmona R, Zhang K, White E, McClements M, Robson AG, Holder GE, Bradshaw K, Hunt DM, Webster AR, Moore AT, Schorderet DF, Munier FL. The PROM1 mutation p.R373C causes an autosomal dominant bull’s eye maculopathy associated with rod, rod-cone, and macular dystrophy. Invest Ophthalmol Vis Sci. 2010;51(9):4771-4780. https://doi.org/10.1167/iovs.09-4561
Corton M, Nishiguchi KM, Avila-Fernández A, Nikopoulos K, Riveiro-Alvarez R, Tatu SD, Ayuso C, Rivolta C. Exome sequencing of index patients with retinal dystrophies as a tool for molecular diagnosis. PLoS One. 2013;8(6):е65574. https://doi.org/10.1371/journal.pone.0065574
Nishiguchi KM, Sandberg MA, Gorji N, Berson EL, Dryja TP. Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. Hum Mutat. 2005;25:248-258.
Kohl S, Baumann B, Broghammer M, Jagle H, Sieving P, Kellner U, Spegal R, Anastasi M, Zrenner E, Sharpe L T, Wissinger B. Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Molec Genet. 2000;9:2107-2116.
Zernant J, Schubert C, Im KM, Burke T, Brown CM, Fishman GA, Tsang SH, Gouras P, Dean M Allikmets R. Analysis of the ABCA4 gene by next-generation sequencing. Invest Ophthalmol Vis Sci. 2011;52:8479-8487.

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