International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias

Brenden Chen, Sharon Whatley, Michael Badminton, Aasne K. Aarsand, Karl Anderson, D. Montgomery Bissell, Herbert L. Bonkovsky, Maria D. Cappellini, Ylva Floderus, Edith C.H. Friesema, Laurent Gouya, Pauline Harper, Raili Kauppinen, Yonina Loskove, Pavel Martásek, John D. Phillips, Hervé Puy, Sverre Sandberg, Caroline Schmitt, Jordi To-FiguerasYedidyah Weiss, Makiko Yasuda, Jean Charles Deybach, Robert J. Desnick

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish (US)
JournalGenetics in Medicine
DOIs
StatePublished - Jan 1 2019

Fingerprint

Porphyrias
Molecular Pathology
Databases
Virulence
Coproporphyrinogen Oxidase
Protoporphyrinogen Oxidase
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
Variegate Porphyria
Hydroxymethylbilane Synthase
Genes
Acute Intermittent Porphyria
Precision Medicine
National Institutes of Health (U.S.)
Heme
Acute Hepatic Porphyria

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 journalArticle

Chen, B, Whatley, S, Badminton, M, Aarsand, AK, Anderson, K, Bissell, DM, Bonkovsky, HL, Cappellini, MD, Floderus, Y, Friesema, ECH, Gouya, L, Harper, P, Kauppinen, R, Loskove, Y, Martásek, P, Phillips, JD, Puy, H, Sandberg, S, Schmitt, C, To-Figueras, J, Weiss, Y, Yasuda, M, Deybach, JC & Desnick, RJ 2019, 'International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias', Genetics in Medicine. https://doi.org/10.1038/s41436-019-0537-7
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. / International Porphyria Molecular Diagnostic Collaborative : an evidence-based database of verified pathogenic and benign variants for the porphyrias. In: Genetics in Medicine. 2019.
@article{1b8a21e956424dc9b013d12a84b7009b,
title = "International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias",
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.",
keywords = "acute hepatic porphyrias, benign variants, database, pathologic variants, variant validation",
author = "Brenden Chen and Sharon Whatley and Michael Badminton and Aarsand, {Aasne K.} and Karl Anderson and Bissell, {D. Montgomery} and Bonkovsky, {Herbert L.} and Cappellini, {Maria D.} and Ylva Floderus and Friesema, {Edith C.H.} and Laurent Gouya and Pauline Harper and Raili Kauppinen and Yonina Loskove and Pavel Mart{\'a}sek and Phillips, {John D.} and Herv{\'e} Puy and Sverre Sandberg and Caroline Schmitt and Jordi To-Figueras and Yedidyah Weiss and Makiko Yasuda and Deybach, {Jean Charles} and Desnick, {Robert J.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41436-019-0537-7",
language = "English (US)",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",

}

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 -