{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:59:54Z","timestamp":1789700394877,"version":"4.0.1"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Turner\u2010type X\u2010linked syndromic intellectual developmental disorder (MRXST) is a neurodevelopmental disorder associated with variants in the\n                    <jats:italic>HUWE1<\/jats:italic>\n                    gene on chromosome Xp11. The condition is characterized by variable phenotypes, including global developmental delay, intellectual disability, and distinctive facial dysmorphisms, with inheritance patterns ranging from X\u2010linked recessive to de novo mutations in females. Here, we describe five probands in two families, highlighting their clinical features and genetic findings. Trio whole\u2010exome sequencing identified a de novo variant in\n                    <jats:italic>HUWE1<\/jats:italic>\n                    in the proband in one family and a maternally inherited hemizygous variant in three boys in a second family. A comprehensive review of\n                    <jats:italic>HUWE1<\/jats:italic>\n                    \u2010associated cases from the literature assisted genotype\u2013phenotype correlations, revealing consistent features such as intellectual disability, skeletal anomalies, and facial dysmorphisms as well as instances of intrafamilial variability. Our findings confirm the phenotypic variability of MRXST and underscore the significance of the\n                    <jats:italic>HUWE1<\/jats:italic>\n                    gene product in neurodevelopment. We propose a baseline monitoring protocol to aid in diagnosis and management, contributing to the development of specific guidelines for patient follow\u2010up.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63959","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T07:00:27Z","timestamp":1733295627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring the Clinical Spectrum of\n                    <scp>\n                      <i>HUWE1<\/i>\n                    <\/scp>\n                    \u2010Related Neurodevelopmental Disorder: Five New Patients and Literature Review"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-1556","authenticated-orcid":false,"given":"Alessandro","family":"De Falco","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine IRCCS Stella Maris Foundation  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5933-3183","authenticated-orcid":false,"given":"Elia Marco Paolo","family":"Minale","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology University Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6574-9608","authenticated-orcid":false,"given":"Camilla","family":"Meossi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine IRCCS Stella Maris Foundation  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Pagano","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine IRCCS Stella Maris Foundation  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5990-5590","authenticated-orcid":false,"given":"Rosanna","family":"Trovato","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine IRCCS Stella Maris Foundation  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-6225","authenticated-orcid":false,"given":"Emanuele","family":"Agolini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda","family":"Mucciolo","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurosciences IRCCS: Scientific Institute for Research, Hospitalization and Healthcare  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-9062","authenticated-orcid":false,"given":"Filippo Maria","family":"Santorelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine IRCCS Stella Maris Foundation  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6117-1974","authenticated-orcid":false,"given":"Carmelo","family":"Piscopo","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetic Unit Antonio Cardarelli Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.11.002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1005"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(94)90120-1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2013.05.005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-024-01576-z"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.7.2819-2831.2005"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-017-0038-6"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200169"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf4802"}],"container-title":["American 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