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

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.

Novel mutation in TENM3 gene in an Iranian patient with Colobomatous Microphthalmia

“…To the best of our knowledge, 7 mutations have been reported in theTENM3 gene in 6 unrelated families, 6 of which are ascribed eye anomalies. Our report would be the 7 th MO and coloboma causative mutation in this gene [2], [26], [28]- [31]. You can see the information of these seven mutations in table 2.…”

“…In addition, Islam et al identified c.1558C>T (a pathogenic homozygous variant) in the TENM3 gene in a patient who was suffering from cataracts, bilateral iris, and chorioretinal colobomas microphthalmia [31].…”

Novel mutation in TENM3 gene in an Iranian patient with colobomatous microphthalmia

“…To the best of our knowledge, seven mutations have been reported in the TENM3 gene in 6 unrelated families, 6 of which are ascribed eye anomalies. Our report would be the 7 th MO and coloboma causative mutation in this gene 2,26,28‐31 . You can see the information of these seven mutations in Table 2.…”

“…Our report would be the 7 th MO and coloboma causative mutation in this gene. 2 , 26 , 28 , 29 , 30 , 31 You can see the information of these seven mutations in Table 2 .…”

“…In addition, Islam et al 31 . identified c.1558C>T (a pathogenic homozygous variant) in the TENM3 gene in a patient who was suffering from cataracts, bilateral iris, and chorioretinal colobomas microphthalmia.…”