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.

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.

journal_name

Hum Mutat

journal_title

Human mutation

authors

Au PYB,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

doi

10.1002/humu.22837

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

1009-1014

issue

10

eissn

1059-7794

issn

1098-1004

journal_volume

36

pub_type

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