GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial dysmorphisms, and skeletal and connective tissue abnormalities caused by de novo variants in HNRNPK

Document Type

Article

Publication Title

Human mutation

Abstract

We report a new syndrome due to loss-of-function variants in the heterogeneous nuclear ribonucleoprotein K gene (HNRNPK). We describe two probands: one with a de novo frameshift (NM_002140.3: c.953+1dup), and the other with a de novo splice donor site variant (NM_002140.3: c.257G>A). Both probands have intellectual disability, a shared unique craniofacial phenotype, and connective tissue and skeletal abnormalities. The identification of this syndrome was made possible by a new online tool, GeneMatcher, which facilitates connections between clinicians and researchers based on shared interest in candidate genes. This report demonstrates that new Web-based approaches can be effective in helping investigators solve exome sequencing projects, and also highlights the newer paradigm of "reverse phenotyping," where characterization of syndromic features follows the identification of genetic variants.

First Page

1009

Last Page

1014

DOI

https://doi.org/10.1002/humu.22837

Publication Date

9-2015

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