{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T18:08:54Z","timestamp":1750442934509,"version":"3.41.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Familial hypercholesterolemia is a treatable genetic condition but remains underdiagnosed. We reviewed the frequency of pathogenic or likely pathogenic (P\/LP) variants in the\n              <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n              gene in female individuals receiving reproductive carrier screening.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              This retrospective observational study included samples from female patients (aged 18\u201355 years) receiving a 274-gene carrier screening panel from January 2020 to September 2022.\n              <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n              exons and their 10 base pair flanking regions were sequenced. Carrier frequency for P\/LP variants was calculated for the entire population and by race\/ethnicity. The most common variants and their likely functional effects were evaluated.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              A total of 91\u2005637 tests were performed on women with race\/ethnicity reported as Asian (8.8%), Black (6.1%), Hispanic (8.5%), White (29.0%), multiple or other (15.0%), and missing (33.0%). Median age was 32.8 years with 83\u2005728 (91%) &lt;40 years. P\/LP\n              <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n              variants were identified in 283 samples (1 in 324). No patients were identified with &gt;1 P\/LP variant.\n              <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n              carrier frequency was higher in Asian (1 in 191 [95% CI, 1 in 142\u2013258]) compared with White (1 in 417 [95% CI, 1 in 326\u2013533];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001) or Black groups (1 in 508 [95% CI, 1 in 284\u2013910];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.004). The most common variants differed between populations. Of all variants, at least 25.0% were predicted as null variants.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              P\/LP variants in\n              <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n              are common. Expanding the use of reproductive carrier screening to include genes associated with FH presents another opportunity to identify people predisposed to cardiovascular disease.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.123.004457","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T09:03:11Z","timestamp":1710925391000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-8179","authenticated-orcid":true,"given":"Vivienne","family":"Souter","sequence":"first","affiliation":[{"name":"Natera, Inc, Austin, TX (V.S., E.B., S.B., B.J.G., B.P., Y.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1628-3938","authenticated-orcid":true,"given":"Emily","family":"Becraft","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX (V.S., E.B., S.B., B.J.G., B.P., Y.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Brummitt","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX (V.S., E.B., S.B., B.J.G., B.P., Y.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2284-8892","authenticated-orcid":true,"given":"Bryan J.","family":"Gall","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX (V.S., E.B., S.B., B.J.G., B.P., Y.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittany","family":"Prigmore","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX (V.S., E.B., S.B., B.J.G., B.P., Y.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Natera, Inc, Austin, TX (V.S., E.B., S.B., B.J.G., B.P., Y.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7917-6946","authenticated-orcid":true,"given":"Peter","family":"Benn","sequence":"additional","affiliation":[{"name":"University of Connecticut Health Center, Farmington, CT (P.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","volume-title":"GeneReviews\u00ae","author":"Ison HE","year":"2014","unstructured":"Ison, HE, Knowles, JW. Familial hypercholesterolemia. In: GeneReviews\u00ae. 2014. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK174884\/"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.02.019"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.05.044"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11748-008-0335-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.06.027"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000297"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1816454"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht273"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.a2423"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000625"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2021.09.012"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01122-3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2020.10.075"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.025192"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01203-z"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgc4.1676"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.316862"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw028"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315904"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf7000"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.06.014"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.193"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.028205"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.520"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03587-X"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.122.003816"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.13044"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000950"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.11.004"},{"key":"e_1_3_3_32_2","unstructured":"Association AH. Familial Hypercholesterolemia (FH). 2020. https:\/\/www.heart.org\/en\/health-topics\/cholesterol\/causes-of-high-cholesterol\/familial-hypercholesterolemia-fh"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001952"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2023.100902"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000005318"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6289"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.12.020"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGEN.123.004457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T21:13:13Z","timestamp":1748553193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.123.004457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1161\/CIRCGEN.123.004457"],"URL":"https:\/\/doi.org\/10.1161\/circgen.123.004457","relation":{},"ISSN":["2574-8300"],"issn-type":[{"type":"electronic","value":"2574-8300"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}