{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:20:39Z","timestamp":1767918039324,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"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":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We recently contributed to the description of eight individuals with a novel condition caused by 16p13.3 microdeletions encompassing <jats:italic>TBC1D24<\/jats:italic>, <jats:italic>ATP6V0C<\/jats:italic>, and <jats:italic>PDPK1<\/jats:italic> and resulting in epilepsy, microcephaly and neurodevelopmental problems. The phenotypic spectrum, the minimum overlapping region and the underlying disease mechanism for this disorder remain to be clarified. Here we report a 3.5\u2010year\u2010old male, with microcephaly, autism spectrum disorder and a de novo 16p13.3 microdeletion. We performed detailed in silico analysis to show that the minimum overlapping region for the condition is ~80Kb encompassing five protein coding genes. Analysis of loss of function constraint metrics, transcript\u2010aware evaluation of the population variants, GeVIR scores, analysis of reported pathogenic point variants, detailed review of the known functions of gene products and their animal models showed that the haploinsufficiency of <jats:italic>ATP6V0C<\/jats:italic> likely underlies the phenotype of this condition. Protein\u2013protein interaction network, gene phenology and analysis of topologically associating domain showed that it was unlikely that the disorder has an epistatic or regulatory basis. 16p13.3 deletions encompassing <jats:italic>ATP6V0C<\/jats:italic> cause a neurodevelopmental disorder. Our results broaden the phenotypic spectrum of this disorder and clarify the likely underlying disease mechanism for the condition.<\/jats:p>","DOI":"10.1002\/ajmg.a.61905","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T07:16:11Z","timestamp":1602227771000},"page":"196-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Haploinsufficiency of <scp><i>ATP6V0C<\/i><\/scp> possibly underlies 16p13.3 deletions that cause microcephaly, seizures, and neurodevelopmental disorder"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7093-8844","authenticated-orcid":false,"given":"Rory J","family":"Tinker","sequence":"first","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St. Mary's Hospital Manchester University Foundation NHS Trust  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George J","family":"Burghel","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St. Mary's Hospital Manchester University Foundation NHS Trust  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shruti","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Neuroscience &amp; Experimental Psychology, School of Biological Sciences University of Manchester  Manchester UK"},{"name":"Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust Greater Manchester Mental Health NHS Trust  Manchester UK"},{"name":"Department of Child and Adolescent Psychiatry Royal Manchester Children's Hospital  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie","family":"Steggall","sequence":"additional","affiliation":[{"name":"Department of Paediatric Medicine Royal Manchester Children's Hospital  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Cuvertino","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine, and Health The University of Manchester  Manchester UK"},{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health The University of Manchester  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8527-2210","authenticated-orcid":false,"given":"Siddharth","family":"Banka","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St. Mary's Hospital Manchester University Foundation NHS Trust  Manchester UK"},{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine, and Health The University of Manchester  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz2924"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0560-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.09.009"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22557"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106528"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204309"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02032-07"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.363549"},{"issue":"2","key":"e_1_2_7_10_1","first-page":"249","article-title":"Rubinstein\u2010Taybi syndrome caused by submicroscopic deletions within 16p13.3","volume":"52","author":"Breuning M. 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