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Here, we report a 3\u2010year\u2010old male patient harboring a hemizygous variant in glypican 4 (<jats:italic>GPC4<\/jats:italic>), which causes Keipert syndrome, who presented with complete lacrimal punctal agenesis, distinctive craniofacial features, mild developmental delay, mild intellectual disability, and autism. The craniofacial features included a prominent forehead, epicanthus, depressed and broad nasal bridge, hypoplastic columella, midface hypoplasia, tented upper lip, and low\u2010set ears. Proband exome sequencing identified a hemizygous variant in <jats:italic>GPC4<\/jats:italic>: NM_001448.3:c.1051C\u2009&gt;\u2009T (p.Arg351*). The <jats:italic>GPC4<\/jats:italic> variant was inherited from his heterozygous mother; X\u2010inactivation followed a skewed pattern in his mother. This patient demonstrated clinical features consistent with Keipert syndrome including craniofacial features, brachydactyly, broad distal phalanx, broad first toe, and mild developmental delay; however, agenesis of the lacrimal puncta has not been reported previously in Keipert syndrome. Our findings suggest that <jats:italic>GPC4<\/jats:italic>, which encodes a heparan\u2010sulfate proteoglycan, may play an important role in lacrimal morphogenesis. Our observations also suggest that Keipert syndrome should be considered in patients with lacrimal punctal agenesis.<\/jats:p>","DOI":"10.1002\/ajmg.a.63799","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T06:09:41Z","timestamp":1719209381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp><i>GPC4<\/i><\/scp> truncating variant associated with Keipert syndrome and lacrimal punctal agenesis"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-6070","authenticated-orcid":false,"given":"Yukiko","family":"Kuroda","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Uehara","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Naruto","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nozomi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-7748","authenticated-orcid":false,"given":"Kenji","family":"Kurosawa","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,23]]},"reference":[{"issue":"6","key":"e_1_2_10_2_1","first-page":"1229","article-title":"Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen\u2010receptor gene correlates with X chromosome inactivation","volume":"51","author":"Allen R. 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