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Recently, rare protein-truncating variants (PTVs) in\n                      <jats:italic>BSN<\/jats:italic>\n                      and\n                      <jats:italic>APBA1<\/jats:italic>\n                      have been implicated as monogenic causes of obesity. Truncating variants in these two genes have been associated with adult-onset monogenic obesity. Here, we aimed to investigate the occurrence of rare PTVs in\n                      <jats:italic>APBA1<\/jats:italic>\n                      and\n                      <jats:italic>BSN<\/jats:italic>\n                      in minors with severe obesity manifesting in early childhood or adolescence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Previously obtained exome data of 209 children and adolescents (0\u201318 years) with severe obesity manifesting in early childhood or adolescence genetically tested at the Ulm University Medical Center between April 2022 and May 2024 were mined for rare PTVs in\n                      <jats:italic>APBA1<\/jats:italic>\n                      (NM_ 001163.4; NP_ NP_001154.2) and\n                      <jats:italic>BSN<\/jats:italic>\n                      (NM_003458.4; NP_003449.2). In all patients, monoallelic, and in the case of autosomal-recessive inheritance, biallelic likely pathogenic and pathogenic variants in well-known obesity-associated genes were excluded. Clinical re-evaluation was performed in two identified cases with rare potentially protein-truncating variants in\n                      <jats:italic>APBA1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The first patient (male, 15 years) presented with a BMI of 33.7 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (BMI z-score: 2.7) after nine years of excessive weight gain despite life-style interventions. He had a body fat percentage of 49.5% and showed hyperphagia. The patient displayed impaired expressive language development, dyslexia and an IQ of 84. His mother also had obesity and dyslexia while his father and younger sister were unaffected. We identified the heterozygous, likely pathogenic variant\n                      <jats:italic>APBA1<\/jats:italic>\n                      :c.814C\u2009&gt;\u2009T;p.(Gln272*) in the index patient and his mother. The second patient (male, 6 years) presented with a BMI of 30.0 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (BMI z-score: 3.8), a body fat percentage of 43.6% and hyperphagia. The child had upslanting palpebral fissures and showed impaired expressive language development. Both parents of the boy were affected by severe obesity and underwent bariatric surgery. We identified the heterozygous variant of unknown significance\n                      <jats:italic>APBA1<\/jats:italic>\n                      :c.2442\u2009+\u20093A\u2009&gt;\u2009C predicted to impair proper splicing in the index patient and his mother.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We conclude that rare potentially protein-truncating variants in\n                      <jats:italic>APBA1<\/jats:italic>\n                      are also found in some minors with early-onset and severe obesity. Therefore, those variants might not be restricted to adult-onset disease. We therefore propose to include\n                      <jats:italic>APBA1<\/jats:italic>\n                      in diagnostic genetic testing for monogenic obesity in minors and adults.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40348-026-00235-2","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:52:36Z","timestamp":1776840756000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protein-truncating variants in APBA1 in minors with severe, early-onset obesity: implications for genetic testing"],"prefix":"10.1186","volume":"13","author":[{"given":"Joanna","family":"Lerner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abubakar","family":"Moawia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Zorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Kloker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"Klehr-Martinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay","family":"Winner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa","family":"Penfold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M. 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The study on genetic causes of obesity in minors was conducted in accordance with the local legislation and institutional requirements and was approved by the Ethics Committee of Ulm University (352\/21). Written informed consent for participation in clinical research including scientific publications was provided by the participants\u2019 legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22"}}