2. Academic Validation
  3. 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

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

  • Hum Mutat. 2015 Oct;36(10):1009-1014. doi: 10.1002/humu.22837.
P Y Billie Au # 1,  Jing You # 2 3,  Oana Caluseriu 4,  Jeremy Schwartzentruber 5,  Jacek Majewski 5,  Francois P Bernier 1 6,  Marcia Ferguson 7,  Care for Rare Canada Consortium,  David Valle 3 8 9,  Jillian S Parboosingh 1 6,  Nara Sobreira 3,  A Micheil Innes # 1 6,  Antonie D Kline # 7
Affiliations

Affiliations

  • 1 Department of Medical Genetics, University of Calgary, Cumming School of Medicine, Alberta, Canada.
  • 2 Predoctoral Training Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 3 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 4 Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
  • 5 Department of Human Genetics, McGill and Genome Quebec Innovation Center, McGill University, Quebec, Canada.
  • 6 Alberta Children's Hospital, Research Institute for Child and Maternal Health, University of Calgary, Alberta, Canada.
  • 7 Harvey Institute for Human Genetics, Department of Pediatrics, Greater Baltimore Medical Center, Baltimore, MD.
  • 8 Center for Inherited Disease Research, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
  • 9 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • # Contributed equally.
PMID: 26173930 DOI: 10.1002/humu.22837
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.

Keywords

GeneMatcher; HNRNPK; WES; matchmaker exchange; reverse phenotyping.

Figures