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Exome sequencing in patients with microphthalmia, anophthalmia, and coloboma ( MAC ) from a consanguineous population
Author(s) -
Islam Farrah,
Htun Stephanie,
Lai LiWen,
Krall Max,
Poranki Menitha,
Martin PierreMarie,
Sobreira Nara,
Wohler Elizabeth S.,
Yu Jingwei,
Moore Anthony T.,
Slavotinek Anne M.
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13830
Subject(s) - anophthalmia , microphthalmia , exome sequencing , genetics , exome , sanger sequencing , disease gene identification , biology , population , single nucleotide polymorphism , consanguinity , coloboma , medicine , bioinformatics , mutation , gene , genotype , environmental health
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.