{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["17(1)"],"submitter":["Chunn LM"],"funding":["Division of Intramural Research, National Institute of Allergy and Infectious Diseases","Inozyme Pharma"],"pubmed_abstract":["<h4>Background</h4>ENPP1 Deficiency-caused by biallelic variants in ENPP1-leads to widespread arterial calcification in early life (Generalized Arterial Calcification of Infancy, GACI) or hypophosphatemic rickets in later life (Autosomal Recessive Hypophosphatemic Rickets type 2, ARHR2). A prior study using the Exome Aggregation Consortium (ExAC)-a database of exomes obtained from approximately 60,000 individuals-estimated the genetic prevalence at approximately 1 in 200,000 pregnancies.<h4>Methods</h4>We estimated the genetic prevalence of ENPP1 Deficiency by evaluating allele frequencies from a population database, assuming Hardy-Weinberg equilibrium. This estimate benefitted from a comprehensive literature review using Mastermind ( https://mastermind.genomenon.com/ ), which uncovered additional variants and supporting evidence, a larger population database with approximately 140,000 individuals, and improved interpretation of variants as per current clinical guidelines.<h4>Results</h4>We estimate a genetic prevalence of approximately 1 in 64,000 pregnancies, thus more than tripling the prior estimate. In addition, the carrier frequency of ENPP1 variants was found to be highest in East Asian populations, albeit based on a small sample.<h4>Conclusion</h4>These results indicate that a significant number of patients with ENPP1 Deficiency remain undiagnosed. Efforts to increase disease awareness as well as expand genetic testing, particularly in non-European populations are warranted, especially now that clinical trials for enzyme replacement therapy, which proved successful in animal models, are underway."],"journal":["Orphanet journal of rare diseases"],"pagination":["421"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9717445"],"repository":["biostudies-literature"],"pubmed_title":["Estimation of ENPP1 deficiency genetic prevalence using a comprehensive literature review and population databases."],"pmcid":["PMC9717445"],"pubmed_authors":["Heinrich SV","Rutsch F","Bissonnette J","Kiel MJ","Ferreira CR","Chunn LM","Mercurio SA"],"additional_accession":[]},"is_claimable":false,"name":"Estimation of ENPP1 deficiency genetic prevalence using a comprehensive literature review and population databases.","description":"<h4>Background</h4>ENPP1 Deficiency-caused by biallelic variants in ENPP1-leads to widespread arterial calcification in early life (Generalized Arterial Calcification of Infancy, GACI) or hypophosphatemic rickets in later life (Autosomal Recessive Hypophosphatemic Rickets type 2, ARHR2). A prior study using the Exome Aggregation Consortium (ExAC)-a database of exomes obtained from approximately 60,000 individuals-estimated the genetic prevalence at approximately 1 in 200,000 pregnancies.<h4>Methods</h4>We estimated the genetic prevalence of ENPP1 Deficiency by evaluating allele frequencies from a population database, assuming Hardy-Weinberg equilibrium. This estimate benefitted from a comprehensive literature review using Mastermind ( https://mastermind.genomenon.com/ ), which uncovered additional variants and supporting evidence, a larger population database with approximately 140,000 individuals, and improved interpretation of variants as per current clinical guidelines.<h4>Results</h4>We estimate a genetic prevalence of approximately 1 in 64,000 pregnancies, thus more than tripling the prior estimate. In addition, the carrier frequency of ENPP1 variants was found to be highest in East Asian populations, albeit based on a small sample.<h4>Conclusion</h4>These results indicate that a significant number of patients with ENPP1 Deficiency remain undiagnosed. Efforts to increase disease awareness as well as expand genetic testing, particularly in non-European populations are warranted, especially now that clinical trials for enzyme replacement therapy, which proved successful in animal models, are underway.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-06-20T03:13:17.782Z","creation":"2025-04-04T13:46:32.32Z"},"accession":"S-EPMC9717445","cross_references":{"pubmed":["36461014"],"doi":["10.1186/s13023-022-02577-2"]}}