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.
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GeneMatcher有助于鉴定出具有智力障碍，独特的面部畸形以及HNRNPK中从头变体引起的骨骼和结缔组织异常的新畸形综合征。
DOI：
10.1002/humu.22837
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发表时间：
2015-10
期刊：
影响因子：
3.9
通讯作者：
Kline AD
中科院分区：
文献类型：
--
作者：
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
我们报告了一个新的综合征由于功能丧失变异的异质核核糖核蛋白K基因（HNRNPK）。我们描述了两个先证者，一个具有从头移码（NM_002140. 3：c.953+1dup），另一个具有从头剪接供体位点变体（NM_002140. 3：c.257G>A）。两个先证者都有智力残疾，共同的独特颅面表型，结缔组织和骨骼异常。一种新的在线工具GeneMatcher使这种综合征的识别成为可能，该工具基于对候选基因的共同兴趣促进了临床医生和研究人员之间的联系。这份报告表明，新的基于网络的方法可以有效地帮助研究人员解决外显子组测序项目，并强调了“反向表型分析”的新范式，其中综合征特征的表征遵循遗传变异的识别。
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.