Abstract
With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information. Therefore, an international collaborative with the European Porphyria Network and the National Institutes of Health/National Center for Advancing Translational Sciences/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NCATS/NIDDK)-sponsored Porphyrias Consortium of porphyria diagnostic experts is establishing an online database that will collate biochemical and clinical evidence verifying the pathogenicity of the published and newly identified variants in the AHP-causing genes. The overall goal of the International Porphyria Molecular Diagnostic Collaborative is to determine the pathogenic and benign variants for all eight porphyrias. Here we describe the overall objectives and the initial efforts to validate pathogenic and benign variants in the respective heme biosynthetic genes causing the AHPs.
| Original language | English (US) |
|---|---|
| Journal | Genetics in Medicine |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- acute hepatic porphyrias
- benign variants
- database
- pathologic variants
- variant validation
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
International Porphyria Molecular Diagnostic Collaborative : an evidence-based database of verified pathogenic and benign variants for the porphyrias. / Chen, Brenden; Whatley, Sharon; Badminton, Michael; Aarsand, Aasne K.; Anderson, Karl; Bissell, D. Montgomery; Bonkovsky, Herbert L.; Cappellini, Maria D.; Floderus, Ylva; Friesema, Edith C.H.; Gouya, Laurent; Harper, Pauline; Kauppinen, Raili; Loskove, Yonina; Martásek, Pavel; Phillips, John D.; Puy, Hervé; Sandberg, Sverre; Schmitt, Caroline; To-Figueras, Jordi; Weiss, Yedidyah; Yasuda, Makiko; Deybach, Jean Charles; Desnick, Robert J.
In: Genetics in Medicine, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - International Porphyria Molecular Diagnostic Collaborative
T2 - an evidence-based database of verified pathogenic and benign variants for the porphyrias
AU - Chen, Brenden
AU - Whatley, Sharon
AU - Badminton, Michael
AU - Aarsand, Aasne K.
AU - Anderson, Karl
AU - Bissell, D. Montgomery
AU - Bonkovsky, Herbert L.
AU - Cappellini, Maria D.
AU - Floderus, Ylva
AU - Friesema, Edith C.H.
AU - Gouya, Laurent
AU - Harper, Pauline
AU - Kauppinen, Raili
AU - Loskove, Yonina
AU - Martásek, Pavel
AU - Phillips, John D.
AU - Puy, Hervé
AU - Sandberg, Sverre
AU - Schmitt, Caroline
AU - To-Figueras, Jordi
AU - Weiss, Yedidyah
AU - Yasuda, Makiko
AU - Deybach, Jean Charles
AU - Desnick, Robert J.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information. Therefore, an international collaborative with the European Porphyria Network and the National Institutes of Health/National Center for Advancing Translational Sciences/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NCATS/NIDDK)-sponsored Porphyrias Consortium of porphyria diagnostic experts is establishing an online database that will collate biochemical and clinical evidence verifying the pathogenicity of the published and newly identified variants in the AHP-causing genes. The overall goal of the International Porphyria Molecular Diagnostic Collaborative is to determine the pathogenic and benign variants for all eight porphyrias. Here we describe the overall objectives and the initial efforts to validate pathogenic and benign variants in the respective heme biosynthetic genes causing the AHPs.
AB - With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information. Therefore, an international collaborative with the European Porphyria Network and the National Institutes of Health/National Center for Advancing Translational Sciences/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NCATS/NIDDK)-sponsored Porphyrias Consortium of porphyria diagnostic experts is establishing an online database that will collate biochemical and clinical evidence verifying the pathogenicity of the published and newly identified variants in the AHP-causing genes. The overall goal of the International Porphyria Molecular Diagnostic Collaborative is to determine the pathogenic and benign variants for all eight porphyrias. Here we describe the overall objectives and the initial efforts to validate pathogenic and benign variants in the respective heme biosynthetic genes causing the AHPs.
KW - acute hepatic porphyrias
KW - benign variants
KW - database
KW - pathologic variants
KW - variant validation
UR - http://www.scopus.com/inward/record.url?scp=85065700023&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065700023&partnerID=8YFLogxK
U2 - 10.1038/s41436-019-0537-7
DO - 10.1038/s41436-019-0537-7
M3 - Article
AN - SCOPUS:85065700023
JO - Genetics in Medicine
JF - Genetics in Medicine
SN - 1098-3600
ER -