{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:17:07Z","timestamp":1783437427231,"version":"3.54.6"},"reference-count":22,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100023917","name":"Englander Precision Medicine Institute at Weill Cornell Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100023917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009515","name":"Manoogian Simone Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>A subset of metabolic diseases is caused by rare monogenic variants. Next-generation sequencing offers a promising approach for identifying such variants, but its application in clinical diagnostics for metabolic disease is limited and the diagnostic yield is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the diagnostic yield of clinical genome sequencing (GS) in adults presenting with common metabolic diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed clinical GS on 560 adults seen in New York clinical practices between August 2020 and December 2023. Participants presented with hyperlipidemia\/hypertriglyceridemia (HLD\/HTG), pre-diabetes, Type 2 diabetes mellitus (T2DM), and\/or metabolic dysfunction-associated fatty liver disease\/steatohepatitis (MAFLD\/MASH). Variants in a curated set of 90 genes associated with monogenic forms of these conditions were classified as Pathogenic (P), Likely Pathogenic (LP), or Variant of Uncertain Significance (VUS) using ACMG\/ClinGen guidelines. P\/LP variants in ACMG secondary findings (v3.1) genes were also reported with participant consent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort had a female-to-male ratio of 1.7, with 18.6% African American and 22.6% Latino participants. The most common enrollment diagnoses were HLD\/HTG (25%), T2DM (9%), pre-diabetes (7%), and MAFLD\/MASH (4%). Many participants had multiple conditions (42% with two, 12% with three). Approximately one-third had reportable variants, with 6% classified as P\/LP. The most common P\/LP variants were in APOB and LDLR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The prevalence of clinically significant (P\/LP) variants related to primary metabolic disease in this cohort was 6%. An additional 5.5% of participants had P\/LP variants in ACMG secondary findings genes. Future studies should refine participant selection for genome sequencing to optimize its diagnostic and clinical value.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jendso\/bvag091","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T11:49:21Z","timestamp":1775735361000},"source":"Crossref","is-referenced-by-count":0,"title":["Genome sequencing identifies monogenic causes in adults with metabolic diseases"],"prefix":"10.1210","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6461-0957","authenticated-orcid":false,"given":"Volkan","family":"Okur","sequence":"first","affiliation":[{"name":"Molecular Diagnostics, New York Genome Center , New York, NY 10013 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7087-7152","authenticated-orcid":false,"given":"Amanda","family":"Marcus","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department 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