Exome sequencing in patients with microphthalmia, anophthalmia, and coloboma (MAC) from a consanguineous population.
Farrah IslamStephanie HtunLi-Wen LaiMax KrallMenitha PorankiPierre-Marie MartinNara SobreiraElizabeth S WohlerJingwei YuAnthony T MooreAnne M SlavotinekPublished in: Clinical genetics (2020)
Next-generation sequencing strategies have resulted in mutation detection rates of 21% to 61% in small cohorts of patients with microphthalmia, anophthalmia and coloboma (MAC), but despite progress in identifying novel causative genes, many patients remain without a genetic diagnosis. We studied a cohort of 19 patients with MAC who were ascertained from a population with high rates of consanguinity. Using single nucleotide polymorphism (SNP) arrays and whole exome sequencing (WES), we identified one pathogenic variant in TENM3 in a patient with cataracts in addition to MAC. We also detected novel variants of unknown significance in genes that have previously been associated with MAC, including KIF26B, MICU1 and CDON, and identified variants in candidate genes for MAC from the Wnt signaling pathway, comprising LRP6, WNT2B and IQGAP1, but our findings do not prove causality. Plausible variants were not found for many of the cases, indicating that our current understanding of the pathogenesis of MAC, a highly heterogeneous group of ocular defects, remains incomplete.
Keyphrases
- copy number
- genome wide
- signaling pathway
- stem cells
- end stage renal disease
- cell proliferation
- ejection fraction
- chronic kidney disease
- newly diagnosed
- epithelial mesenchymal transition
- emergency department
- gene expression
- oxidative stress
- peritoneal dialysis
- loop mediated isothermal amplification
- electronic health record
- optic nerve