International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias.
acute hepatic porphyrias
benign variants
database
pathologic variants
variant validation
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
28
02
2019
accepted:
26
04
2019
pubmed:
11
5
2019
medline:
28
4
2020
entrez:
11
5
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31073229
doi: 10.1038/s41436-019-0537-7
pii: S1098-3600(21)01067-4
pmc: PMC7229570
mid: NIHMS1583774
doi:
Substances chimiques
Porphobilinogen Synthase
EC 4.2.1.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2605-2613Subventions
Organisme : NCATS NIH HHS
ID : U2C TR002818
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK083909
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK110858
Pays : United States
Références
Anderson KE, Sassa S, Bishop DF, Desnick RJ. Disorders of heme biosynthesis: X-linked sideroblastic anemia and the porphyrias. In: Beaudet AL, Vogelstein B, Kinzler KW, et al., eds. The online metabolic and molecular bases of inherited disease. New York, NY: McGraw-Hill; 2014. https://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62638866#1102890723 . Accessed 8 May 2019.
Puy H, Gouya L, Deybach JC. Porphyrias. Lancet. 2010;375:924–937.
doi: 10.1016/S0140-6736(09)61925-5
Bonkovsky HL, Maddukuri VC, Yazici C, et al. Acute porphyrias in the USA: features of 108 subjects from porphyrias consortium. Am J Med. 2014;127:1233–1241.
doi: 10.1016/j.amjmed.2014.06.036
pubmed: 4563803
pmcid: 4563803
Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017;377:862–872.
doi: 10.1056/NEJMra1608634
Bonkovsky HL, Guo JT, Hou W, Li T, Narang T, Thapar M. Porphyrin and heme metabolism and the porphyrias. Compr Physiol. 2013;3:365–401.
pubmed: 23720291
Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005;142:439–450.
doi: 10.7326/0003-4819-142-6-200503150-00010
Aarsand AK, Petersen PH, Sandberg S. Estimation and application of biological variation of urinary delta-aminolevulinic acid and porphobilinogen in healthy individuals and in patients with acute intermittent porphyria. Clin Chem. 2006;52:650–656.
doi: 10.1373/clinchem.2005.060772
Woolf J, Marsden JT, Degg T, et al. Best practice guidelines on first-line laboratory testing for porphyria. Ann Clin Biochem. 2017;54:188–198.
doi: 10.1177/0004563216667965
Zhang J, Yasuda M, Desnick RJ, Balwani M, Bishop D, Yu C. A LC-MS/MS method for the specific, sensitive, and simultaneous quantification of 5-aminolevulinic acid and porphobilinogen. J Chromatogr B Analyt Technol Biomed Life Sci. 2011;879:2389–2396.
doi: 10.1016/j.jchromb.2011.06.034
pubmed: 3269068
pmcid: 3269068
Whatley SD, Badminton MN. Role of genetic testing in the management of patients with inherited porphyria and their families. Ann Clin Biochem. 2013;50:204–216.
doi: 10.1177/0004563212473278
The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526:68–74.
doi: 10.1038/nature15393
pubmed: 4750478
pmcid: 4750478
Lek M, Karczewski KJ, Minikel EV, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–291.
doi: 10.1038/nature19057
pubmed: 5018207
pmcid: 5018207
Stenson PD, Mort M, Ball EV, et al. The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum Genet. 2017;136:665–677.
doi: 10.1007/s00439-017-1779-6
pubmed: 5429360
pmcid: 5429360
Chen B, Solis-Villa C, Hakenberg J, et al. Acute intermittent porphyria: predicted pathogenicity of HMBS variants indicates extremely low penetrance of the autosomal dominant disease. Hum Mutat. 2016;37:1215–1222.
doi: 10.1002/humu.23067
pubmed: 5063710
pmcid: 5063710
Puy H, Deybach JC, Lamoril J, et al. Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria. Am J Hum Genet. 1997;60:1373–1383.
doi: 10.1086/515455
pubmed: 1716106
pmcid: 1716106
Robreau-Fraolini AM, Puy H, Aquaron C, et al. Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms. Hum Genet. 2000;107:150–159.
doi: 10.1007/s004390000323
Solis C, Martinez-Bermejo A, Naidich TP, et al. Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias. Arch Neurol. 2004;61:1764–1770.
doi: 10.1001/archneur.61.11.1764
Tandy-Connor S, Guiltinan J, Krempely K, et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med. 2018;20:1515–1521.
doi: 10.1038/gim.2018.38
pubmed: 6301953
pmcid: 6301953
Friez MJ. Attention: direct-to-consumer patrons: proceed with caution. Genet Med. 2018;20:1508–1509.
doi: 10.1038/s41436-018-0030-8
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–424.
doi: 10.1038/gim.2015.30
pubmed: 4544753
pmcid: 4544753
Ellard S, Baple EL, Owens M, et al. ACGS Best Practice Guidelines for Variant Classification. 2018. http://www.acgs.uk.com/media/1092626/uk_practice_guidelines_for_variant_classification_2017.pdf . Accessed 27 July 2018.
Ellard S, Baple EL, Owens M, et al. ACGS Best Practice Guidelines for Variant Classification. 2017. http://www.acgs.uk.com/media/1140458/uk_practice_guidelines_for_variant_classification_2018_v1.0.pdf .
Cotton RG, Al Aqeel AI, Al-Mulla F, et al. Capturing all disease-causing mutations for clinical and research use: toward an effortless system for the Human Variome Project. Genet Med. 2009;11:843–849.
doi: 10.1097/GIM.0b013e3181c371c5
pubmed: 20010362
pmcid: 20010362
Johnston JJ, Biesecker LG. Databases of genomic variation and phenotypes: existing resources and future needs. Hum Mol Genet. 2013;22:R27–R31.
doi: 10.1093/hmg/ddt384
pubmed: 3782073
pmcid: 3782073
Bennetts B, Caramins M, Hsu A, et al. Quality standards for DNA sequence variation databases to improve clinical management under development in Australia. Appl Transl Genom. 2014;3:54–57.
doi: 10.1016/j.atg.2014.07.002
pubmed: 4888016
pmcid: 4888016
Adams DR, Eng CM. Next-generation sequencing to diagnose suspected genetic disorders. N Engl J Med. 2018;379:1353–1362.
doi: 10.1056/NEJMra1711801
Milko LV, Funke BH, Hershberger RE, et al. Development of Clinical Domain Working Groups for the Clinical Genome Resource (ClinGen): lessons learned and plans for the future. Genet Med. 2019;21:987–993.
doi: 10.1038/s41436-018-0267-2
den Dunnen JT, Dalgleish R, Maglott DR, et al. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat. 2016;37:564–569.
doi: 10.1002/humu.22981
Whatley SD, Mason NG, Woolf JR, Newcombe RG, Elder GH, Badminton MN. Diagnostic strategies for autosomal dominant acute porphyrias: retrospective analysis of 467 unrelated patients referred for mutational analysis of the HMBS, CPOX, or PPOX gene. Clin Chem. 2009;55:1406–1414.
doi: 10.1373/clinchem.2008.122564
Marsden JT, Rees DC. Urinary excretion of porphyrins, porphobilinogen and delta-aminolaevulinic acid following an attack of acute intermittent porphyria. J Clin Pathol. 2014;67:60–65.
doi: 10.1136/jclinpath-2012-201367
Balwani M, Wang B, Anderson KE, et al. Acute hepatic porphyrias: recommendations for evaluation and long-term management. Hepatology. 2017;66:1314–1322.
doi: 10.1002/hep.29313
pubmed: 5605422
pmcid: 5605422
Hift RJ, Davidson BP, van der Hooft C, Meissner DM, Meissner PN. Plasma fluorescence scanning and fecal porphyrin analysis for the diagnosis of variegate porphyria: precise determination of sensitivity and specificity with detection of protoporphyrinogen oxidase mutations as a reference standard. Clin Chem. 2004;50:915–923.
doi: 10.1373/clinchem.2003.025213
Nordmann Y, Puy H. Human hereditary hepatic porphyrias. Clin Chim Acta. 2002;325:17–37.
doi: 10.1016/S0009-8981(02)00276-0
Guo R, Lim CK, Peters TJ. Accurate and specific HPLC assay of coproporphyrinogen III oxidase activity in human peripheral leucocytes. Clin Chim Acta. 1988;177:245–252.
doi: 10.1016/0009-8981(88)90069-1
Guo R, Lim CK, Peters TJ. High-performance liquid chromatographic assays for protoporphyrinogen oxidase and ferrochelatase in human leucocytes. J Chromatogr. 1991;566:383–396.
doi: 10.1016/0378-4347(91)80255-B
Schmitt C, Gouya L, Malonova E, et al. Mutations in human CPO gene predict clinical expression of either hepatic hereditary coproporphyria or erythropoietic harderoporphyria. Hum Mol Genet. 2005;14:3089–3098.
doi: 10.1093/hmg/ddi342
Mustajoki P. Normal erythrocyte uroporphyrinogen I synthase in a kindred with acute intermittent porphyria. Ann Intern Med. 1981;95:162–166.
doi: 10.7326/0003-4819-95-2-162
McColl KE, Moore MR, Thompson GG, Goldberg A. Screening for latent acute intermittent porphyria: the value of measuring both leucocyte delta-aminolaevulinic acid synthase and erythrocyte uroporphyrinogen-1-synthase activities. J Med Genet. 1982;19:271–276.
doi: 10.1136/jmg.19.4.271
pubmed: 1048892
pmcid: 1048892
Bonaiti-Pellie C, Phung L, Nordmann Y. Recurrence risk estimation of acute intermittent porphyria based on analysis of porphobilinogen deaminase activity: a Bayesian approach. Am J Med Genet. 1984;19:755–762.
doi: 10.1002/ajmg.1320190415
Lamon JM, Frykholm BC, Tschudy DP. Family evaluations in acute intermittent porphyria using red cell uroporphyrinogen I synthetase. J Med Genet. 1979;16:134–139.
doi: 10.1136/jmg.16.2.134
pubmed: 1012738
pmcid: 1012738
Meissner PN, Day RS, Moore MR, Disler PB, Harley E. Protoporphyrinogen oxidase and porphobilinogen deaminase in variegate porphyria. Eur J Clin Invest. 1986;16:257–261.
doi: 10.1111/j.1365-2362.1986.tb01339.x
Lamoril J, Puy H, Whatley SD, et al. Characterization of mutations in the CPO gene in British patients demonstrates absence of genotype-phenotype correlation and identifies relationship between hereditary coproporphyria and harderoporphyria. Am J Hum Genet. 2001;68:1130–1138.
doi: 10.1086/320118
pubmed: 1226094
pmcid: 1226094
Mustajoki P, Desnick RJ. Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland. Br Med J (Clin Res Ed). 1985;291:505–509.
doi: 10.1136/bmj.291.6494.505
Yasuda M, Chen B, Desnick RJ. Recent advances on porphyria genetics: inheritance, penetrance & molecular heterogeneity, including new modifying/causative genes. Mol Genet Metab. 2018;S1096-7192:30645.
Grandchamp B, De Verneuil H, Beaumont C, Chretien S, Walter O, Nordmann Y. Tissue-specific expression of porphobilinogen deaminase. Two isoenzymes from a single gene. Eur J Biochem. 1987;162:105–110.
doi: 10.1111/j.1432-1033.1987.tb10548.x
pubmed: 3816774
pmcid: 3816774
Chen CH, Astrin KH, Lee G, Anderson KE, Desnick RJ. Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes “variant acute intermittent porphyria” with normal expression of the erythroid-specific enzyme. J Clin Invest. 1994;94:1927–1937.
doi: 10.1172/JCI117543
pubmed: 294605
pmcid: 294605
Lenglet H, Schmitt C, Grange T, et al. From a dominant to an oligogenic model of inheritance with environmental modifiers in acute intermittent porphyria. Hum Mol Genet. 2018;27:1164–1173.
doi: 10.1093/hmg/ddy030
Riera C, Lois S, de la Cruz X. Prediction of pathological mutations in proteins: the challenge of integrating sequence conservation and structure stability principles. WIREs Comput Mol Sci. 2014;4:249–268.
doi: 10.1002/wcms.1170
Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. Predicting the functional effect of amino acid substitutions and indels. PLoS ONE. 2012;7:e46688.
doi: 10.1371/journal.pone.0046688
pubmed: 3466303
pmcid: 3466303