{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T16:33:10Z","timestamp":1776443590952,"version":"3.51.2"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pettigrew syndrome (PGS), an X\u2010linked intellectual disability (XLID), is caused by mutations in the <jats:italic>AP1S2<\/jats:italic> gene. Herein, we described a Thai family with six patients who had severe\u2010to\u2010profound intellectual impairment, limited verbal communication, and varying degrees of limb spasticity. One patient had a unilateral cataract. We demonstrated facial evolution over time, namely coarse facies, long faces, and thick lip vermilions. We identified a novel <jats:italic>AP1S2<\/jats:italic> variant, c.1\u20102A&gt;G. The mRNA analysis revealed that the variant resulted in splicing defects with leaky splicing, yielding two distinct aberrant transcripts, one of which likely resulting in the mutant protein lacking the first 44 amino acids whereas the other possibly leading to no production of the protein. By performing a literature review, we found 51 patients and 11 <jats:italic>AP1S2<\/jats:italic> pathogenic alleles described and that all the variants were loss\u2010of\u2010function alleles. The severity of ID in Pettigrew syndrome is mostly severe\u2010to\u2010profound (54.8%), followed by moderate (26.2%) and mild. Progressive spasticity was noted in multiple patients. In summary, leaky splicing found in the present family was likely related to the intrafamilial clinical variability. Our data also support the previous notion of variable expression and neuroprogressive nature of the disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.63639","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T12:29:41Z","timestamp":1714393781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel <scp><i>AP1S2<\/i><\/scp> variant causing leaky splicing in X\u2010linked intellectual disability: Further delineation and intrafamilial variability"],"prefix":"10.1002","volume":"194","author":[{"given":"Saisuda","family":"Noojarern","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-7993","authenticated-orcid":false,"given":"Thipwimol","family":"Tim\u2010Aroon","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kingthong","family":"Anurat","sequence":"additional","affiliation":[{"name":"Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital Mahidol University  Samut Prakan Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Phetthong","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Phramongkutklao Hospital and Phramongkutklao College of Medicine  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthaporn","family":"Khongkraparn","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-2176","authenticated-orcid":false,"given":"Duangrurdee","family":"Wattanasirichaigoon","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2011.12.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20531"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.135"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.14633"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-8628(19990730)85:3\u27e8266::aid-ajmg16\u27e93.0.co;2-p"},{"issue":"1","key":"e_1_2_9_7_1","first-page":"36","article-title":"Challenges in molecular diagnosis of X\u2010linked intellectual disability","volume":"133","author":"De Luca C.","year":"2020","journal-title":"British Medical Bulletin"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1972.tb04274.x"},{"issue":"3","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.1221","article-title":"A novel splice site mutation in AP1S2 gene for X\u2010linked mental retardation in a Chinese pedigree and literature review","volume":"9","author":"Huo L.","year":"2019","journal-title":"Brain and Behavior: A Cognitive Neuroscience Perspective"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2012.02800.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38710"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320380206"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.051334"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.7.535"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/510137"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.01074"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-69633-4"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10005"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.5"},{"issue":"1110","key":"e_1_2_9_22_1","first-page":"11.10.1","article-title":"From FastQ data to high confidence variant calls: The genome analysis toolkit best practices pipeline","volume":"43","author":"Van der Auwera G. 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