Individual with Homozygous TECR Variant Expands Upon the Existing Phenotype for a Hutterite Founder Mutation

Abstract

Intellectual disability (ID) is ubiquitous across nations affecting roughly 1 percent of the world's population. Improvements in genetic testing methodologies have led to increased understanding about the etiology of ID. However, many cases remain idiopathic. We describe the first individual outside of an existing sibship with a homozygous TECR variant; c.545C>T. Similar to the previously described sibship, this individual is of Hutterite ancestry; suggesting that TECR-related ID is due to a founder mutation. The phenotypic spectrum is expanded to include dolicocephaly and dysgenesis of the corpus callosum. First-tier genetic testing (chromosomal microarray) identified multiple regions of homozygosity (ROH); however, the diagnosis was made by second-tier sequencing in a gene outside of any ROH. The authors advocate for the use of second-tier sequencing in cases of ID in the absence of major congenital anomalies or the presence of consanguinity and/or a limited gene pool. At the very least, sequencing of the TECR gene should be included in the diagnostic workup for individuals with Hutterite ancestry presenting with ID.