{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:24:38Z","timestamp":1786955078903,"version":"build-2736575974"},"reference-count":13,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Peroxisomal fatty acyl\u2010CoA reductase 1 (FAR1) deficiency is a rare single\u2010enzyme peroxisomal disorder caused by biallelic pathogenic variants in FAR1, typically manifesting with severe neurodevelopmental delay, hypotonia, early\u2010onset epilepsy, and congenital cataracts. We report a male infant born to first\u2010cousin parents presenting with severe global developmental delay, refractory seizures, progressive microcephaly, and feeding difficulties, together with a previously unreported finding of imperforate anus. Ophthalmologic examination revealed abnormal macular reflexes without overt cataracts. Brain MRI at 14\u2009months showed diffuse bilateral subcortical and periventricular T2\/FLAIR hyperintensities consistent with chronic white matter disease. Metabolic screening was normal. Rhizomelic chondrodysplasia punctata was excluded, and whole\u2010exome sequencing identified a homozygous likely pathogenic canonical splice\u2010site variant (NM_032228.3:c.\u20107\u20102A&gt;G) in\n                    <jats:italic>FAR1<\/jats:italic>\n                    . Functional cDNA analysis confirmed skipping of exon 2, supporting a loss\u2010of\u2010function mechanism. Segregation analysis confirmed autosomal recessive inheritance. This single\u2010case observation raises the possibility that the phenotypic spectrum of FAR1 deficiency may extend to gastrointestinal malformations such as imperforate anus, highlights the limitations of routine biochemical testing, and underscores the importance of early whole\u2010exome sequencing for definitive diagnosis and multidisciplinary management.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70272","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:39:33Z","timestamp":1786952373000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expansion of the Clinical Spectrum of Autosomal Recessive Fatty Acyl\u2010\n                    <scp>CoA<\/scp>\n                    Reductase 1 (\n                    <i>FAR1<\/i>\n                    ) Deficiency: A Previously Unreported Association With Imperforate Anus\u2014A Case Report"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6833-5313","authenticated-orcid":false,"given":"Mostafa Ibraheem Abo","family":"Alrob","sequence":"first","affiliation":[{"name":"Palestine Polytechnic University  Hebron Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8214-394X","authenticated-orcid":false,"given":"Fawaz","family":"Awad","sequence":"additional","affiliation":[{"name":"Istishari Arab Hospital  Ramallah Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9665-0641","authenticated-orcid":false,"given":"Ranya Abu","family":"Khalaf","sequence":"additional","affiliation":[{"name":"Palestine Polytechnic University  Hebron Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanin","family":"Kassem","sequence":"additional","affiliation":[{"name":"Istishari Arab Hospital  Ramallah Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha Nizar","family":"Azar","sequence":"additional","affiliation":[{"name":"Ibn Sina Specialized Hospital  Jenin Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Abuhajji","sequence":"additional","affiliation":[{"name":"Ibn Sina Specialized Hospital  Jenin Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Mallah","sequence":"additional","affiliation":[{"name":"Ibn Sina Specialized Hospital  Jenin Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-9957","authenticated-orcid":false,"given":"Imad","family":"Dweikat","sequence":"additional","affiliation":[{"name":"Metabolic Department, Faculty of Medicine Arab American University  Jenin Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"e6307","DOI":"10.1002\/ccr3.6307","article-title":"Milder Presentation of Autosomal Dominant Fatty Acyl CoA Reductase 1\u2010Related Syndrome: Report of the First Middle Eastern Patient and Review of the Literature","volume":"10","author":"Almuqbil M.","year":"2022","journal-title":"Clinical Case Reports"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13073-022-01087-x","article-title":"A Systematic Analysis of Splicing Variants Identifies New Diagnoses in the 100,000 Genomes Project","volume":"14","author":"Blakes A. 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J.","year":"2014","journal-title":"Cell Metabolism"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"689892","DOI":"10.3389\/fgene.2021.689892","article-title":"Splicing in the Diagnosis of Rare Disease: Advances and Challenges","volume":"12","author":"Lord J.","year":"2021","journal-title":"Frontiers in Genetics"},{"key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00439-017-1821-8","article-title":"The Landscape of Genetic Diseases in Saudi Arabia Based on the First 1000 Diagnostic Panels and Exomes","volume":"136","author":"Monies D.","year":"2017","journal-title":"Human Genetics"},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/cge.13934","article-title":"A Rare Case of Fatty Acyl\u2010CoA Reductase 1 Deficiency in an Indian Infant Manifesting Rhizomelic Chondrodystrophy Phenotype","volume":"99","author":"Radha Rama Devi A.","year":"2021","journal-title":"Clinical Genetics"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards S.","year":"2015","journal-title":"Genetics in Medicine"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s12098-023-04652-3","article-title":"Complex Hereditary Spastic Paraparesis Caused by de Novo p.Arg480Ser in FAR1","volume":"91","author":"Shambhavi A.","year":"2024","journal-title":"Indian Journal of Pediatrics"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.15844\/pedneurbriefs-29-1-5","article-title":"Fatty Acyl\u2010CoA Reductase 1 Deficiency","volume":"29","author":"Swisher C. N.","year":"2015","journal-title":"Pediatr Neurol Briefs"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70272","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:39:35Z","timestamp":1786952375000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":13,"alternative-id":["10.1002\/ajmg.a.70272"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70272","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"assertion":[{"value":"2026-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70272"}}