Targeted Next-Generation sequencing in anophthalmia and microphthalmia patients confirms SOX2, OTX2 and FOXE3 mutationsReportar como inadecuado

Targeted Next-Generation sequencing in anophthalmia and microphthalmia patients confirms SOX2, OTX2 and FOXE3 mutations - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Medical Genetics

, 12:172

Genetic epidemiology and genetic associations


BackgroundAnophthalmia-microphthalmia A-M is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A-M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A-M.

MethodsWe used a pooled sequencing design, together with custom single nucleotide polymorphism SNP calling software. We verified predicted sequence alterations using Sanger sequencing.

ResultsWe verified three mutations - c.542delC in SOX2, resulting in p.Pro181Argfs*22, p.Glu105X in OTX2 and p.Cys240X in FOXE3. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic - p.Glu42Lys in CRYBA4, p.Val201Met in FOXE3 and p.Asp291Asn in VSX2. Our analysis methodology gave one false positive result comprising a mutation in PAX6 c.1268A > T, predicting p.X423LeuextX*15 that was not verified by Sanger sequencing. We also failed to detect one 20 base pair bp deletion and one 3 bp duplication in SOX2.

ConclusionsOur results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A-M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10-15 patients and conclude that there is a need for further gene discovery in A-M.

Keywordsanophthalmia microphthalmia next-generation sequencing SOX2 OTX2 FOXE3 Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-12-172 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Nelson Lopez Jimenez - Jason Flannick - Mani Yahyavi - Jiang Li - Tanya Bardakjian - Leath Tonkin - Adele Schneider - Ellio


Documentos relacionados