{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:15:03Z","timestamp":1770822903276,"version":"3.50.1"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[1995,6]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            Cholesterol ester storage disease (CESD) is associated with premature atherosclerosis, hepatomegaly, elevated LDL cholesterol levels, and in most cases, low HDL cholesterol levels. Previous studies have shown a G\u2192A mutation at the 3\u2032 splice junction of exon 8 (E8SJM) of the gene encoding lysosomal acid lipase (LAL) in two kindreds with CESD. In a Canadian-Norwegian kindred with this disease, we show this mutation in conjunction with an as yet unknown T\u2192C transition in exon 10 predicting a Leu\n            <jats:sub>336<\/jats:sub>\n            \u2192Pro (L336P) replacement and an A\u2192C transversion in exon 2 predicting a T-6P replacement in the prepeptide. Identification of the L336P rather than the T-6P replacement as the second defect underlying CESD in our patient is deduced from three lines of evidence. First, the E8SJM allele is located in\n            <jats:italic>cis<\/jats:italic>\n            with the mutation predicting the T-6P\u2013encoding allele but in\n            <jats:italic>trans<\/jats:italic>\n            with the L336P-encoding allele; second, the L336P but not the T-6P replacement cosegregates with low LAL activity in the family; third, the T-6P replacement was found in 6 of 28 alleles from subjects with normal lysosomal acid lipase activity, suggesting that this variant represents a frequent nonfunctional polymorphism. Since the residual LAL activity is higher and the clinical phenotype based on plasma lipid values and severity of hepatosplenomegaly is milder in this case than in a previously studied case who was homozygous for the E8SJM allele, we conclude that the L336P variant appears to be associated with a phenotypically mild form of CESD.\n          <\/jats:p>","DOI":"10.1161\/01.atv.15.6.773","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"773-778","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["A Novel Variant of Lysosomal Acid Lipase (Leu\n            <sub>336<\/sub>\n            \u2192Pro) Associated With Acid Lipase Deficiency and Cholesterol Ester Storage Disease"],"prefix":"10.1161","volume":"15","author":[{"given":"Udo","family":"Seedorf","sequence":"first","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiko","family":"Wiebusch","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandro","family":"Muntoni","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels C.","family":"Christensen","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flemming","family":"Skovby","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Nickel","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Roskos","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Funke","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leiv","family":"Ose","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Assmann","sequence":"additional","affiliation":[{"name":"From the Institut fu\u0308r Arterioskleroseforschung (U.S., H.W., S.M., V.N., M.R., H.F., G.A.) and the Institut fu\u0308r Klinische Chemie und Laboratoriumsmedizin (S.M., H.F., G.A.), Zentrallaboratorium, Westfa\u0308lische Wilhelms-Universita\u0308t, Germany; the Department of Pediatrics (N.C.C.), S\u00f8nderborg Sygehus, S\u00f8nderborg, Denmark; the Department of Pediatrics (F.S.), Rigshospitalet, Copenhagen, Denmark; and the Lipid Clinic (L.O.), Rikshospitalet, Oslo, Norway."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Assmann G Seedorf U. 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New York NY: McGraw-Hill. 1995:2563-2587."},{"key":"e_1_3_2_2_2","first-page":"718","volume":"58","year":"1963","journal-title":"Ann Intern Med"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"8487","DOI":"10.1016\/S0021-9258(19)40786-2","volume":"250","year":"1975","journal-title":"J Biol Chem"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"22479","DOI":"10.1016\/S0021-9258(18)54597-X","volume":"266","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1052"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1180"},{"key":"e_1_3_2_7_2","first-page":"2713","volume":"92","year":"1994","journal-title":"J Clin Invest"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00223858"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1016\/S0021-9258(18)93349-1","volume":"243","year":"1968","journal-title":"J Biol Chem"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(72)28114-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/S0022-2275(20)34756-8","volume":"21","year":"1980","journal-title":"J Lipid Res"},{"key":"e_1_3_2_12_2","first-page":"298","volume":"11","year":"1991","journal-title":"Biotechniques"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.13.4937"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2718"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/20.7.1717"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.14.4008"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00591a005"},{"key":"e_1_3_2_18_2","first-page":"1409","volume":"69","year":"1972","journal-title":"Proc Natl Acad Sci U S A"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/13.6.1891"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4781(87)90083-2"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00218a022"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360220105"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01805475"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.ATV.15.6.773","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T14:08:52Z","timestamp":1647526132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.ATV.15.6.773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,6]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1995,6]]}},"alternative-id":["10.1161\/01.ATV.15.6.773"],"URL":"https:\/\/doi.org\/10.1161\/01.atv.15.6.773","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,6]]}}}