The ClinGen Congenital Disorders of Glycosylation Gene Curation Expert Panel
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical Genetics
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Secondary Categories:
- Clinical Genetics
Introduction:
Congenital disorders of glycosylation (CDG) are a genetically and clinically heterogeneous group of >200 diseases caused by defects in various steps in glycan synthesis, attachment, and modification pathways. In general, diseases fall into four categories: those affecting N-linked glycosylation, those affecting O-linked glycosylation, those affecting lipid glycosylation, and those that may affect multiple glycosylation pathways (including, but not limited to, dolichol metabolism, Golgi transport/homeostasis, and sialic acid metabolism). Here we report the progress in clinical validity assessment of CDG-related genes by the Clinical Genome Resource (ClinGen) Congenital Disorders of Glycosylation (CDG) gene curation expert panel (GCEP).
Methods:
188 genes were initially identified as involved in CDG by CDG researchers and physicians affiliated with the Rare Disease Clinical Research Network (RDCRN) Frontiers in CDG Consortium (FCDGC), and correlated to commercially available CDG panels. The gene list is continually being evaluated to identify new appropriate candidate genes. The GCEP consists of 2 coordinators, 2 chairs, 12 experts and 6 active biocurators (as well as 6 former biocurators). The CDG GCEP was approved as an expert panel in March of 2023. Biocurators assess the relationship of each gene to the asserted CDG(s) using the ClinGen Gene-Disease Validity framework. Genes were classified as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. Gene-level evidence was presented on bimonthly calls and classification reached by consensus. Approved curations were then published to the ClinGen website.
Results:
Using the ClinGen Gene-Disease Validity framework, the CDG GCEP has curated 35 gene-disease associations, with 15 Definitive, 3 Strong, 10 Moderate, and 7 Limited classifications. This equates to 18% of the initial 188-gene list. The GCEP approves approximately 4 new curations per month, which are then published to the ClinGen website.
Conclusion:
The CDG GCEP has made significant contributions to the understanding of gene-disease relationships under the CDG umbrella. This effort has also helped identify genes with little published data available that would benefit from more case publications.
Congenital disorders of glycosylation (CDG) are a genetically and clinically heterogeneous group of >200 diseases caused by defects in various steps in glycan synthesis, attachment, and modification pathways. In general, diseases fall into four categories: those affecting N-linked glycosylation, those affecting O-linked glycosylation, those affecting lipid glycosylation, and those that may affect multiple glycosylation pathways (including, but not limited to, dolichol metabolism, Golgi transport/homeostasis, and sialic acid metabolism). Here we report the progress in clinical validity assessment of CDG-related genes by the Clinical Genome Resource (ClinGen) Congenital Disorders of Glycosylation (CDG) gene curation expert panel (GCEP).
Methods:
188 genes were initially identified as involved in CDG by CDG researchers and physicians affiliated with the Rare Disease Clinical Research Network (RDCRN) Frontiers in CDG Consortium (FCDGC), and correlated to commercially available CDG panels. The gene list is continually being evaluated to identify new appropriate candidate genes. The GCEP consists of 2 coordinators, 2 chairs, 12 experts and 6 active biocurators (as well as 6 former biocurators). The CDG GCEP was approved as an expert panel in March of 2023. Biocurators assess the relationship of each gene to the asserted CDG(s) using the ClinGen Gene-Disease Validity framework. Genes were classified as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. Gene-level evidence was presented on bimonthly calls and classification reached by consensus. Approved curations were then published to the ClinGen website.
Results:
Using the ClinGen Gene-Disease Validity framework, the CDG GCEP has curated 35 gene-disease associations, with 15 Definitive, 3 Strong, 10 Moderate, and 7 Limited classifications. This equates to 18% of the initial 188-gene list. The GCEP approves approximately 4 new curations per month, which are then published to the ClinGen website.
Conclusion:
The CDG GCEP has made significant contributions to the understanding of gene-disease relationships under the CDG umbrella. This effort has also helped identify genes with little published data available that would benefit from more case publications.