{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:09:17Z","timestamp":1788804557245,"version":"build-2803163510"},"reference-count":54,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education Russian Federation","award":["075-15-2025-489"],"award-info":[{"award-number":["075-15-2025-489"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>FLAD1<\/jats:italic>\n                    gene codes for flavin adenine dinucleotide (FAD) synthase. FAD is a cofactor for many redox enzymes involved in vital processes from respiration to signal transduction. In this work, we described a clinical case of 2 siblings carrying compound heterozygous mutations in the\n                    <jats:italic>FLAD1<\/jats:italic>\n                    gene resulting in the substitutions A418V and R542* at the protein level. The patients demonstrate adrenal insufficiency, which has not previously been associated with FLAD1 protein defects. To verify that adrenal insufficiency is caused by\n                    <jats:italic>FLAD1<\/jats:italic>\n                    mutations, we created a personalized mouse model carrying the mutations found in the patients. The mutation in the\n                    <jats:italic>FLAD1<\/jats:italic>\n                    gene, leading to the A418V substitution, appeared viable in the homozygous state, with minimal difference from the WT. The\n                    <jats:italic>FLAD1<\/jats:italic>\n                    gene mutation leading to the R542* truncation is lethal when homozygous. The mouse model of the compound heterozygous\n                    <jats:italic>FLAD1<\/jats:italic>\n                    <jats:sup>A418V\/R542*<\/jats:sup>\n                    mutations recapitulated the physiological, biochemical, and endocrine manifestations of\n                    <jats:italic>FLAD1<\/jats:italic>\n                    mutations in patients. The mouse model created demonstrates the causal effect of FLAD1 mutations on the described pathology and potentially paves the way for understanding the disease\u2019s molecular mechanism and developing better therapies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.198799","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:01:06Z","timestamp":1788804066000},"source":"Crossref","is-referenced-by-count":0,"title":["A familial case of FLAD1 protein deficiency associated with impaired adrenal steroidogenesis"],"prefix":"10.1172","volume":"11","author":[{"given":"Olga A.","family":"Averina","sequence":"first","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia Yu.","family":"Kalinchenko","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre, Moscow, 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S.","family":"Buev","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia."},{"name":"Center for Bio- and Medical Technologies, Skolkovo Institute of Science and Technology, Skolkovo, Russia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina A.","family":"Guseva","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia."},{"name":"Faculty of Chemistry, Lomonosov Moscow State University, Moscow, Russia."},{"name":"Center for Bio- and Medical Technologies, Skolkovo Institute of Science and Technology, Skolkovo, Russia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia V.","family":"Priymak","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia."},{"name":"Faculty 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