{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T23:00:55Z","timestamp":1780354855660,"version":"3.54.1"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The development of hypertriglyceridemia (HTG) can be attributed to either a monogenic or a polygenic etiologic basis, and the understanding of this molecular basis is incomplete. APOA5 plays a critical role in triglyceride (TG) metabolism, and APOA5 deficiency is a recognized cause of HTG. However, the effects of rare\n                      <jats:italic>APOA5<\/jats:italic>\n                      variants observed only in isolated cases are often difficult to establish conclusively. This study aims to find the genetic cause of moderate HTG in a Chinese family, and conduct preliminary\n                      <jats:italic>in silico<\/jats:italic>\n                      verification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eight family members received biochemical testing, and genetic testing based on whole-exome sequencing (WES). Basic information including body mass index (BMI), medical history, prescription for TG management, and smoking and drinking habits was recorded. Comprehensive residue conservation analysis and computational simulation of protein structure stability were performed to measure the impact of the assumptive causal variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A rare heterozygous\n                      <jats:italic>APOA5<\/jats:italic>\n                      variant (p.R223C) was identified. Specifically, six family members who carried the variant had substantially higher fasting plasma TG level than the admitted threshold (1.7\u00a0mmol\/L) with the highest of 4.96\u00a0mmol\/L, while a non-carrier in this family was normal in TG. The p. R223C variant was absent from ClinVar and gnomAD databases. Besides,\n                      <jats:italic>in silico<\/jats:italic>\n                      predictions results supported the variant\u2019s potential deleteriousness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study presents a familial case of moderate HTG associated with a rare\n                      <jats:italic>APOA5<\/jats:italic>\n                      variant, which is classified as Likely Pathogenic (LP) according to the ACMG\/AMP guideline. The real effect of this variant requires further investigation via biochemical or cell-based studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1796970","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:10:54Z","timestamp":1780351854000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular characterization of a rare heterozygous APOA5 variant in a Chinese family with moderate hypertriglyceridemia"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongxia","family":"Liu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Jishou University","place":["Jishou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yuan","sequence":"additional","affiliation":[{"name":"China Regional Research Centre, International Centre for Genetic Engineering and Biotechnology","place":["Taizhou, Jiangsu, China"]},{"name":"Guangzhou BroadBio Technology Co., Ltd.","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jishou University","place":["Jishou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuande","family":"Mao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jishou University","place":["Jishou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxi","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongli","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jishou University","place":["Jishou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Tian","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jishou University","place":["Jishou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yili","family":"Yang","sequence":"additional","affiliation":[{"name":"China Regional Research Centre, International Centre for Genetic Engineering and Biotechnology","place":["Taizhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xiang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jishou University","place":["Jishou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1002\/humu.23626","article-title":"ClinGen sequence variant interpretation working G: recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion","volume":"39","author":"Abou Tayoun","year":"2018","journal-title":"Hum. 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