Exome sequencing in patients with microphthalmia, anophthalmia, and coloboma (MAC) from a consanguineous population.

TitleExome sequencing in patients with microphthalmia, anophthalmia, and coloboma (MAC) from a consanguineous population.
Publication TypeJournal Article
Year of Publication2020
AuthorsIslam, F, Htun, S, Lai, L-W, Krall, M, Poranki, M, Martin, P-M, Sobreira, N, Wohler, ES, Yu, J, Moore, AT, Slavotinek, AM
JournalClin Genet
Date Published2020 Aug 15
ISSN1399-0004
Abstract

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.

DOI10.1111/cge.13830
Alternate JournalClin. Genet.
PubMed ID32799327
Grant ListNHGRI UM1 HG006542 / / National Human Genome Research Institute, National Institutes of Health /
/ / research allocation program (RAP) Team science award /