{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:52:55Z","timestamp":1789203175762,"version":"build-2803163510"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Autosomal recessive familial hypercholesterolemia (ARH) is a very rare lipid metabolic monogenic disorder caused by homozygosity or compound heterozygosity for mutations in the low-density lipoprotein receptor adapter protein 1 (<jats:italic>LDLRAP1<\/jats:italic>) gene. It is a life-threatening disease characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, and premature coronary artery disease. Membranous nephropathy (MN) is less commonly observed in children. Here, the co-existence of ARH and MN was diagnosed in a Chinese girl.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>We present the case of a 13-year-old girl who was admitted with the typical symptom of nephrotic syndrome with an abnormally high serum LDL-C level. Gene sequencing revealed a novel homozygous <jats:italic>LDLRAP1<\/jats:italic> variant (NM_015627: c.383 T&amp;gt;G, p.V128G), and the patient was diagnosed with ARH. A renal biopsy suggested that the nephrotic syndrome in the girl was induced by MN, but no evidence of secondary MN was found. A thorough examination was performed to explore the association between MN and ARH. Medical management with angiotensin receptor blockers and aggressive lipid-lowering treatment led to remission of proteinuria and clinical condition stabilization during 2-year follow-up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first case of co-existence of MN and ARH in a teenager carrying a novel pathogenic mutation of the <jats:italic>LDLRAP1<\/jats:italic> gene (NM_015627: c.383 T&amp;gt;G, p.V128G).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.811317","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T07:33:04Z","timestamp":1643959984000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Autosomal Recessive Hypercholesterolemia Caused by a Novel LDLRAP1 Variant and Membranous Nephropathy in a Chinese Girl: A Case Report"],"prefix":"10.3389","volume":"9","author":[{"given":"Siqin","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1093\/eurheartj\/ehu274","article-title":"Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society","volume":"35","author":"Cuchel","year":"2014","journal-title":"Eur Heart J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3478","DOI":"10.1093\/eurheartj\/eht273","article-title":"Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society","volume":"34","author":"Nordestgaard","year":"2013","journal-title":"Eur Heart J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41572-021-00303-z","article-title":"Membranous nephropathy","volume":"7","author":"Ronco","year":"2021","journal-title":"Nat Rev Dis Primers."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/S0140-6736(82)91513-6","article-title":"Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease","volume":"2","author":"Moorhead","year":"1982","journal-title":"Lancet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s11906-012-0250-2","article-title":"Lipid nephrotoxicity: new concept for an old disease","volume":"14","author":"Gyebi","year":"2012","journal-title":"Curr Hypertens Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3389\/fphys.2019.00280","article-title":"Current status of familial hypercholesterolemia in China: a need for patient FH registry systems","volume":"10","author":"Chen","year":"2019","journal-title":"Front Physiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1038\/ki.2012.486","article-title":"Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy","volume":"83","author":"Kanigicherla","year":"2013","journal-title":"Kidney Int."},{"key":"B8","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1038\/ki.1994.349","article-title":"Lipids and the kidney","volume":"46","author":"Keane","year":"1994","journal-title":"Kidney Int."},{"key":"B9","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrneph.2017.155","article-title":"Dyslipidaemia in nephrotic syndrome: mechanisms and treatment","volume":"14","author":"Agrawal","year":"2018","journal-title":"Nat Rev Nephrol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1097\/MOL.0b013e32833c1ef6","article-title":"Marked HDL deficiency and premature coronary heart disease","volume":"21","author":"Schaefer","year":"2010","journal-title":"Curr Opin Lipidol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"15090","DOI":"10.1074\/jbc.M008466200","article-title":"Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice","volume":"276","author":"Lambert","year":"2001","journal-title":"J Biol Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1007\/s00467-007-0534-y","article-title":"case of homozygous familial hypercholesterolemia with focal segmental glomerulosclerosis","volume":"22","author":"Elmaci","year":"2007","journal-title":"Pediatr Nephrol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3278","DOI":"10.1172\/JCI37950","article-title":"The ARH adaptor protein regulates endocytosis of the ROMK potassium secretory channel in mouse kidney","volume":"119","author":"Fang","year":"2009","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1038\/s41467-020-15383-w","article-title":"The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis","volume":"11","author":"J.","year":"2020","journal-title":"Nat Commun"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.811317\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T07:33:07Z","timestamp":1643959987000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.811317\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,4]]},"references-count":14,"alternative-id":["10.3389\/fcvm.2022.811317"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.811317","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,4]]},"article-number":"811317"}}