{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:34:06Z","timestamp":1792373646056,"version":"4.4.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"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. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We proposed that the deficit of ACC1 is the cause of patient symptoms including global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. We evaluated the possible disease-causing role of the <jats:italic>ACACA<\/jats:italic> gene in developmental delay and investigated the pathogenesis of ACC1 deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A patient who presented with global developmental delay with unknown cause was recruited. Detailed medical records were collected and reviewed. Whole exome sequencing found two variants of <jats:italic>ACACA<\/jats:italic> with unknown significance. ACC1 mRNA expression level, protein expression level, and enzyme activity level were detected in patient-derived cells. Lipidomic analysis, and <jats:italic>in vitro<\/jats:italic> functional studies including cell proliferation, apoptosis, and the migratory ability of patient-derived cells were evaluated to investigate the possible pathogenic mechanism of ACC1 deficiency. RNAi-induced ACC1 deficiency fibroblasts were established to assess the causative role of ACC1 deficit in cell migratory disability in patient-derived cells. Palmitate supplementation assays were performed to assess the effect of palmitic acid on ACC1 deficiency-induced cell motility deficit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient presented with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. A decreased level of ACC1 and ACC1 enzyme activity were detected in patient-derived lymphocytes. Lipidomic profiles revealed a disruption in the lipid homeostasis of the patient-derived cell lines. <jats:italic>In vitro<\/jats:italic> functional studies revealed a deficit of cell motility in patient-derived cells and the phenotype was further recapitulated in ACC1-knockdown (KD) fibroblasts. The cell motility deficit in both patient-derived cells and ACC1-KD were attenuated by palmitate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report an individual with biallelic mutations in <jats:italic>ACACA<\/jats:italic>, presenting global development delay. <jats:italic>In vitro<\/jats:italic> studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2021.618492","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T05:07:47Z","timestamp":1630904867000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Biallelic Mutations in ACACA Cause a Disruption in Lipid Homeostasis That Is Associated With Global Developmental Delay, Microcephaly, and Dysmorphic Facial Features"],"prefix":"10.3389","volume":"9","author":[{"given":"Xiaoting","family":"Lou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangpeng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhu","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiqiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hezhi","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1073\/pnas.97.4.1444","article-title":"The subcellular localization of acetyl-CoA carboxylase 2.","volume":"97","author":"Abu-Elheiga","year":"2000","journal-title":"Proc. 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