{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:46:47Z","timestamp":1785836807130,"version":"3.56.0"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["15\u2010HG\u20100130"],"award-info":[{"award-number":["15\u2010HG\u20100130"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Long\u2010chain 3\u2010hydroxyacyl\u2010CoA dehydrogenase deficiency (LCHADD) is an autosomal recessive mitochondrial defect of long\u2010chain fatty acid \u03b2\u2010oxidation, caused by biallelic pathogenic variants in\n                    <jats:italic>HADHA<\/jats:italic>\n                    or\n                    <jats:italic>HADHB<\/jats:italic>\n                    . We report a 22\u2010year\u2010old male with an atypically mild presentation of LCHADD who was referred to the Undiagnosed Diseases Network (UDN). Trio genome sequencing identified a maternally inherited\n                    <jats:italic>HADHA<\/jats:italic>\n                    frameshift pathogenic variant and a paternally inherited noncoding rare\n                    <jats:italic>HADHA<\/jats:italic>\n                    variant. The paternal noncoding variant was predicted by in silico splicing analysis to create a cryptic splice donor site. This was experimentally confirmed to partially perturb splicing, leading to partial disruption of normal splicing and the production of both normal and aberrant transcripts. Transcripts derived from the cryptic donor site were subject to nonsense\u2010mediated decay (NMD). As a result, the proband's cells produced three\n                    <jats:italic>HADHA<\/jats:italic>\n                    transcripts: a truncated maternal transcript that was destroyed by NMD, an abnormally spliced paternal transcript also subject to NMD, and a normally spliced paternal transcript. The presence of residual normally spliced\n                    <jats:italic>HADHA<\/jats:italic>\n                    transcripts from the paternal allele likely contributes to partial preservation of LCHAD enzyme function and provides a plausible explanation for the proband's attenuated clinical phenotype.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70172","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T07:52:57Z","timestamp":1777276377000},"page":"2128-2135","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Odyssey of Atypical Long\u2010Chain 3\u2010Hydroxyacyl\u2010\n                    <scp>CoA<\/scp>\n                    Dehydrogenase Deficiency (\n                    <scp>LCHADD<\/scp>\n                    ) Explained by Three Allelic Products From Two Pathogenic Variants"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7278-8242","authenticated-orcid":false,"given":"Yutaka","family":"Furuta","sequence":"first","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette C.","family":"Rives","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3805-7606","authenticated-orcid":false,"given":"T. Andrew","family":"Burrow","sequence":"additional","affiliation":[{"name":"Section of Genetics and Metabolism, Department of Pediatrics University of Arkansas for Medical Sciences, College of Medicine  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3522-2135","authenticated-orcid":false,"given":"Thomas A.","family":"Cassini","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7093-8844","authenticated-orcid":false,"given":"Rory J.","family":"Tinker","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Genomics Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy K.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7200-7644","authenticated-orcid":false,"given":"Kimberly M.","family":"Ezell","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwan","family":"Hamid","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy D.","family":"Cogan","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"John A.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010013\u20109628\u20109"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010022\u201002358\u2010x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61558"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.1.99"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63383"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010024\u201003423\u20103"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.0b013e318232a005"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.13313"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010015\u20100236\u20107"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010018\u20100875\u20106"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgc4.1091"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001242\u20106"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.70053"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010022\u201002598\u2010x"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2025.109283"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2025.101398"},{"key":"e_1_2_13_18_1","first-page":"1993","volume-title":"GeneReviews","author":"Prasun 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