[Stargardt病的分子遗传学诊断]

[Molecular genetic diagnosis of Stargardt disease].

作者信息

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

机构信息

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

Voronezh Regional Clinical Consultative and Diagnostic Center, 5a Lenina Sq., Voronezh, Russia, 394018.

出版信息

Vestn Oftalmol. 2017;133(4):4-11. doi: 10.17116/oftalma201713344-11.

DOI:10.17116/oftalma201713344-11

PMID:28980559

Abstract

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.

摘要