Panel ‐based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns

ConclusionThis study highlights that panel‐based WES is a reliable and effective strategy for the genetic diagnosis of MA. Furthermore, using this technique, the mutational spectrum of these diseases was broadened, with novel variants identified in each of the OTX2, PAX6, and RBP4 genes. Moreover, we report new cases of reduced penetrance, mosaicism, and variable phenotypic expressivity associated with MA, further demonstrating the heterogeneity of such disorders.

We evaluated the implementation of whole exome sequencing (WES) for the genetic analysis of a panel in which all dominant, recessive, and X‐linked MA candidates were included. We identified three novel missense mutations associated with MA, as well as cases of reduced penetrance, mosaicism, and variable phenotypic expressivity associated with the conditions. The analysis not only demonstrates the utility of panel‐based WES for diagnosing the molecular basis of MA, but also provides further evidence of the heterogeneity of these disorders, highlighting the significant challenges associated with genetic counseling.

Source: Molecular Genetics & Genomic Medicine - August 21, 2017 Category: Genetics & Stem Cells Authors: Marina Riera, Ana Wert, Isabel Nieto, Esther Pomares Tags: Original Article Source Type: research