{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:39:51Z","timestamp":1790098791807,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T00:00:00Z","timestamp":1518393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Adaptor protein complex\u20104 (AP\u20104) is a heterotetrameric protein complex which plays a key role in vesicle trafficking in neurons. Mutations in genes affecting different subunits of AP\u20104, including <jats:italic>AP4B1<\/jats:italic>, <jats:italic>AP4E1<\/jats:italic>, <jats:italic>AP4S1<\/jats:italic>, and <jats:italic>AP4M1<\/jats:italic>, have been recently associated with an autosomal recessive phenotype, consisting of spastic tetraplegia, and intellectual disability (ID). The overlapping clinical picture among individuals carrying mutations in any of these genes has prompted the terms \u201cAP\u20104 deficiency syndrome\u201d for this clinically recognizable phenotype. Using whole\u2010exome sequencing, we identified a novel homozygous mutation (c.991C&gt;T, p.Q331*, NM_006594.4) in <jats:italic>AP4B1<\/jats:italic> in two siblings from a consanguineous Pakistani couple, who presented with severe ID, progressive spastic tetraplegia, epilepsy, and microcephaly. Sanger sequencing confirmed the mutation was homozygous in the siblings and heterozygous in the parents. Similar to previously reported individuals with <jats:italic>AP4B1<\/jats:italic> mutations, brain MRI revealed ventriculomegaly and white matter loss. Interestingly, in addition to the typical facial gestalt reported in other AP\u20104 deficiency cases, the older brother presented with congenital left Horner syndrome, bilateral optic nerve atrophy and cataract, which have not been previously reported in this condition. In summary, we report a novel <jats:italic>AP4B1<\/jats:italic> homozygous mutation in two siblings and review the phenotype of AP\u20104 deficiency, speculating on a possible role of AP\u20104 complex in eye development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38628","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T09:52:40Z","timestamp":1518429160000},"page":"985-991","source":"Crossref","is-referenced-by-count":15,"title":["A novel homozygous <i>AP4B1<\/i> mutation in two brothers with AP\u20104 deficiency syndrome and ocular anomalies"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8724-6721","authenticated-orcid":false,"given":"Andrea","family":"Accogli","sequence":"first","affiliation":[{"name":"Department of Pediatrics McGill University Montreal Canada"},{"name":"Istituto Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi 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