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GLSP is caused by either biallelic or heterozygous, dominant\u2010negative, pathogenic variants in\n                    <jats:italic>ITPR1<\/jats:italic>\n                    . Here, we present a 5\u2010year\u2010old male with GLSP who was found to have a heterozygous, de novo intronic variant in\n                    <jats:italic>ITPR1<\/jats:italic>\n                    (NM_001168272.1:c.5935\u201017G\u2009&gt;\u2009A) through genome sequencing (GS). Sanger sequencing of cDNA from this individual's fibroblasts showed the retention of 15 nucleotides from intron 45, which is predicted to cause an in\u2010frame insertion of five amino acids near the C\u2010terminal transmembrane domain of ITPR1. In addition, qPCR and cDNA sequencing demonstrated reduced expression of both\n                    <jats:italic>ITPR1<\/jats:italic>\n                    alleles in fibroblasts when compared to parental samples. Given the close proximity of the predicted in\u2010frame amino acid insertion to the site of previously described heterozygous, de novo, dominant\u2010negative, pathogenic variants in GLSP, we predict that this variant also has a dominant\u2010negative effect on ITPR1 channel function. Overall, this is the first report of a de novo intronic variant causing GLSP, which emphasizes the utility of GS and cDNA studies for diagnosing patients with a clinical presentation of GLSP and negative clinical exome sequencing.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62232","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T08:36:44Z","timestamp":1620203804000},"page":"2315-2324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A novel de novo intronic variant in\n                    <scp>\n                      <i>ITPR1<\/i>\n                    <\/scp>\n                    causes Gillespie syndrome"],"prefix":"10.1002","volume":"185","author":[{"given":"Laura","family":"Keehan","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas 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 Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Murdock","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4177-709X","authenticated-orcid":false,"given":"Pengfei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Baylor Genetics  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill V.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Radiology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason 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