GeneMatcher

Au PY, You J, Caluseriu O, Schwartzentruber J, Majewski J, Bernier FP,
Ferguson M; Care for Rare Canada Consortium, Valle D, Parboosingh JS, Sobreira N,
Innes AM, Kline AD. GeneMatcher Aids in the Identification of a New Malformation
Syndrome with Intellectual Disability, Unique Facial Dysmorphisms, and Skeletal
and Connective Tissue Caused by de novo Variants in HNRNPK. Hum Mutat. 2015 Jul
14.

 

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.