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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
Author(s) -
Au P. Y. Billie,
You Jing,
Caluseriu Oana,
Schwartzentruber Jeremy,
Majewski Jacek,
Bernier Francois P.,
Ferguson Marcia,
Valle David,
Parboosingh Jillian S.,
Sobreira Nara,
Innes A. Micheil,
Kline Antonie D.
Publication year - 2015
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22837
Subject(s) - biology , proband , genetics , intellectual disability , exome sequencing , frameshift mutation , genetic heterogeneity , kabuki syndrome , phenotype , identification (biology) , facial dysmorphism , craniofacial , bioinformatics , gene , computational biology , mutation , botany
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.