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: Vestnik Oftalmologii. 2017;133(4): 4‑11

DOI: 10.17116/oftalma201713344-11

Downloaded: 11

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. Vestnik Oftalmologii. 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

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