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Jinu Han, Seung-Tae Lee; Next generation sequencing reveal accurate molecular diagnosis in patients with infantile nystagmus syndrome. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2784.
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© ARVO (1962-2015); The Authors (2016-present)
Infantile nystagmus syndrome (INS) is genetically heterogeneous disorders including Leber congenital amaurosis, achromatopsia, foveal hypoplasia, ocular albinism and idiopathic form. This study assessed the utility of integrating genomic data from next-generation sequencing and phenotypic data to enhance the firm diagnosis of INS.
A total of 24 patients diagnosed with INS were selected for investigation through a single institution. Mutations were detected using a custom-designed target enrichment that permitted parallel analysis of 114 genes associated with INS by high-throughput, next-generation DNA sequencing (NGS). Suspected pathogenic variants were confirmed by bidirectional Sanger sequencing in relevant probands and other affected family members.
We identified mutated alleles that were highly likely to be causative in 15 of the 24 patients, achieving a 62.5% molecular diagnostic rate. Among the 15 patients, 5 had autosomal dominant disease, 7 had autosomal recessive disease, and 3 had X-linked disease. Family history of nystagmus consistent with X-linked inheritance was found in 3 patients. Two patients were found to have GPR143 mutation and 1 had FRMD7 mutation. Family history of autosomal dominant inheritance was noted in 2 patients. One had PAX6 mutation and no pathogenic mutation was found in the other. Among 19 patients with no family history of nystagmus, 3 patients were CNGA3 mutation, 3 were PAX6 mutation, 1 had CEP290 mutation, 1 had RPGRIP1 mutation, 1 had NMNAT1 mutation, 1 had SPATA7 mutation, and 1 had OPA1 mutation. The phenotypes of these patients were consistent with genotypes.
NGS methods can detect disease-causing genetic variants in 62.5% of consecutive patients referred for evaluation of a possible genetic condition. Therefore, NGS can be used to differentiate the causes in patients with INS because hand-held optical coherence tomography and electroretinogram are not easily applicable to young infant.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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