{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:59:00Z","timestamp":1790402340981,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Very long\u2010chain fatty acids (VLCFAs) composed of more than 20 carbon atoms are essential in the biosynthesis of cell membranes in the brain, skin, and retina. VLCFAs are elongated beyond 28 carbon atoms by ELOVL4 enzyme. Variants in <jats:italic>ELOVL4<\/jats:italic> are associated with three Mendelian disorders: autosomal dominant (AD) Stargardt\u2010like macular dystrophy type 3, AD spinocerebellar ataxia, and autosomal recessive disorder congenital ichthyosis, spastic quadriplegia and impaired intellectual development (ISQMR). Only seven subjects from five unrelated families with ISQMR have been described, all of which have biallelic single\u2010nucleotide variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed clinical exome sequencing on probands from four unrelated families with neuro\u2010ichthyosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three novel homozygous <jats:italic>ELOVL4<\/jats:italic> variants. Two of the families originated from the same Saudi tribe and had the exact homozygous exonic deletion in <jats:italic>ELOVL4<\/jats:italic>, while the third and fourth probands had two different novel homozygous missense variants. Seven out of the eight affected subjects had profound developmental delay, epilepsy, axial hypotonia, peripheral hypertonia, and ichthyosis. Delayed myelination and corpus callosum hypoplasia were seen in two of five subjects with brain magnetic rosonance imaging and cerebral atrophy in three.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study expands the allelic spectrum of <jats:italic>ELOVL4\u2010<\/jats:italic>related ISQMR. The detection of the same exonic deletion in two unrelated Saudi family from same tribe suggests a tribal founder mutation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2256","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T17:09:13Z","timestamp":1692637753000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Expanding the allelic spectrum of <i>ELOVL4<\/i>\u2010related autosomal recessive neuro\u2010ichthyosis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0052-8163","authenticated-orcid":false,"given":"Fatima","family":"Alabdulrazzaq","sequence":"first","affiliation":[{"name":"Department of Pediatrics Adan Hospital, Ministry of Health  Hadiya Kuwait"},{"name":"Kuwait Institute of Medical Specialization  Sulaibkikhat 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