{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:55:50Z","timestamp":1792166150200,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23DK119949"],"award-info":[{"award-number":["K23DK119949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hypophosphatasia (HPP) is an underrecognized, complex bone mineralization disorder with variable manifestations caused by one or two deleterious variants in the alkaline phosphatase (\n                    <jats:italic>ALPL<\/jats:italic>\n                    ) gene. Expanded carrier screening (ECS), inclusive of\n                    <jats:italic>ALPL<\/jats:italic>\n                    , intends to inform reproductive risk but may incidentally reveal an HPP diagnosis with 50% familial risks. We sought to investigate at\u2010risk individuals and develop a multidisciplinary referral and evaluation protocol for ECS\u2010identified\n                    <jats:italic>ALPL<\/jats:italic>\n                    heterozygosity. A retrospective database query of ECS results from 8\u2009years to 1\u2009month for heterozygous pathogenic\/likely pathogenic\n                    <jats:italic>ALPL<\/jats:italic>\n                    \u00a0variants was completed. We implemented a clinical protocol for diagnostic testing and imaging, counseling, and interdisciplinary care management for identified patients, and outcomes were documented. Heterozygous\n                    <jats:italic>ALPL<\/jats:italic>\n                    variants were identified in 12\/2248 unrelated patients undergoing ECS (0.53%; heterozygote frequency 1\/187). Of 10 individuals successfully contacted, all demonstrated symptomatology and\/or alkaline phosphatase values consistent with HPP. ECS may reveal incidental health risks, including recognition of missed HPP diagnoses in\n                    <jats:italic>ALPL<\/jats:italic>\n                    heterozygotes. In our cohort, all ECS\u2010identified\n                    <jats:italic>ALPL<\/jats:italic>\n                    heterozygotes with clinical and\/or biochemical data available demonstrated features of HPP. Referral to a genetics professional familiar with HPP is indicated for family history assessment, genetic counseling, cascade testing, and long\u2010term bone health management.\n                  <\/jats:p>","DOI":"10.1002\/mgg3.2056","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T03:50:48Z","timestamp":1669693848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Not just a carrier: Clinical presentation and management of patients with heterozygous disease\u2010causing alkaline phosphatase (\n                    <i>ALPL<\/i>\n                    ) variants identified through expanded carrier screening"],"prefix":"10.1002","volume":"11","author":[{"given":"Natalie M.","family":"Beck","sequence":"first","affiliation":[{"name":"Greenberg Center for Skeletal Dysplasias, Department Genetic of Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Genome Medical Services  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9812-771X","authenticated-orcid":false,"given":"Katelynn G.","family":"Sagaser","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"JunoDx  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathleen S.","family":"Lawson","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Hertenstein","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Jachens","sequence":"additional","affiliation":[{"name":"Center for Maternal and Fetal Medicine Howard County General Hospital, Johns Hopkins Hospital  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine R.","family":"Forster","sequence":"additional","affiliation":[{"name":"Center for Fetal Therapy Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Sibley Memorial Hospital Maternal Fetal Medicine  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8567-3850","authenticated-orcid":false,"given":"Kristen A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-4029","authenticated-orcid":false,"given":"Angie C.","family":"Jelin","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin J.","family":"Blakemore","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Hoover\u2010Fong","sequence":"additional","affiliation":[{"name":"Greenberg Center for Skeletal Dysplasias, Department Genetic of Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31711"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr\u20102015\u2010212827"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010015\u20103272\u20101"},{"key":"e_1_2_15_5_1","unstructured":"Blakemore K. Sagaser K. G. Hoover\u2010Fong J. Beck N. Lawson C. Leppert K. Hertenstein C. Forster K. R. Trebes S. &Jelin A. C.(2019).Fool me once: The dilemma of fetal long bone bowing. [Oral presentation]. In38th Annual International Fetal Medicine & Surgery Society Meeting Sils Switzerland."},{"key":"e_1_2_15_6_1","volume-title":"Identifier NCT0230672, an observational, longitudinal, prospective, long\u2010term registry of patients with hypophosphatasia (HPP)","author":"ClinicalTrials.gov","year":"2014"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2011.177741"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001951"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001952"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24010"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000666"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr\u20102020\u2010234764"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102350\u201010\u201051"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6033"},{"key":"e_1_2_15_15_1","unstructured":"Genetic Information Nondiscrimination Act of 2008. 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G. Jelin A. C. Hoover\u2010Fong J. Beck N. Lawson C. S. Leppert K. Hertenstein C. Forster K. R. Trebes S. &Blakemore K.(2019).Autosomal dominant hypophosphatasia (HPP): A condition overlooked on expanded carrier screening?InPoster presented at the 23rd International Conference on Prenatal Diagnosis and Therapy Singapore."},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.33176\/AACB\u201019\u201000031"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.01.045"},{"key":"e_1_2_15_36_1","unstructured":"Strensiq. 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