{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:07Z","timestamp":1753869727505,"version":"3.41.2"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lenz\u2010Majewski syndrome (LMS) is a rare genetic disorder characterized by osteosclerosis, intellectual disability, characteristic facies, and distinct craniofacial, dental, cutaneous, and distal\u2010limb anomalies. Mutations in the <jats:italic>PTDSS1<\/jats:italic> gene, which encodes one of the phosphatidylserines (PS) synthase enzymes, PSS1, have been identified as causative in LMS patients. These mutations make PSS1 insensitive to feedback inhibition by PS levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole genome sequence (WGS) was performed on a patient with congenital <jats:italic>cutis laxa<\/jats:italic> and her parents. PS synthase activity was analyzed in <jats:italic>PTDSS1<\/jats:italic> mutant cDNA clones to evaluate functional alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 5\u2010year\u2010old girl presented with congenital skin wrinkles and was initially diagnosed with congenital <jats:italic>cutis laxa<\/jats:italic>. She had bilateral inner ear hypoplasia, bilateral low\u2010frequency hearing loss, attention\u2010deficit\/hyperactivity disorder, and mild intellectual disability. Physical examination revealed protruding ears, frontal bossing, and dental malalignment. A <jats:italic>de novo<\/jats:italic> heterozygous missense variant in the <jats:italic>PTDSS1<\/jats:italic> gene, c.284G&gt;A (p. Arg95Gln) was identified by WGS. Functional analysis indicated increased PS synthase activity, supporting the pathogenicity of this variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The patient's <jats:italic>cutis laxa<\/jats:italic> and facial features were consistent with LMS, though radiographic findings did not reveal the characteristic sclerosing bone dysplasia reported in previous cases. This observation suggests that LMS may have a broader phenotypic spectrum than previously recognized.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70112","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T07:30:16Z","timestamp":1750145416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Japanese Case of Lenz\u2010Majewski Syndrome With a Novel <i>PTDSS1<\/i> Variant"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8629-2435","authenticated-orcid":false,"given":"Yasuko","family":"Kobari","sequence":"first","affiliation":[{"name":"Department of AI and Innovative Medicine Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Department of Pediatrics Gunma University Graduate School of Medicine  Maebashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5766-8771","authenticated-orcid":false,"given":"Non","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology National Institute of Infectious Diseases  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of AI and Innovative Medicine Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Saijo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohisa","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeo","family":"Kure","sequence":"additional","affiliation":[{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Miyagi Children's Hospital  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuo","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Department of Pediatrics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen","family":"Tamiya","sequence":"additional","affiliation":[{"name":"Department of AI and Innovative Medicine Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gunma University Graduate School of Medicine  Maebashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61327"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2015"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.11"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0030-4220(69)90026-7"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-007-0165-y"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.148.7.2207"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2014.10.014"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.149.1.6611917"},{"issue":"1","key":"e_1_2_11_10_1","first-page":"115","article-title":"Cutis Laxa, Skeletal Anomalies, and Ambiguous Genitalia","volume":"127","author":"Kaye C. 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