{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:46:29Z","timestamp":1788173189097,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,18]],"date-time":"2023-06-18T00:00:00Z","timestamp":1687046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017691","name":"Guangxi Key Research and Development Program","doi-asserted-by":"publisher","award":["GuikeAB17195004"],"award-info":[{"award-number":["GuikeAB17195004"]}],"id":[{"id":"10.13039\/501100017691","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":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Homozygous or compound heterozygous <jats:italic>ROBO3<\/jats:italic> gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 <jats:italic>ROBO3<\/jats:italic> mutations have been identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We described an HGPPS patient and performed whole\u2010exome sequencing (WES) to identify the causative gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a missense variant and a splice\u2010site variant in the <jats:italic>ROBO3<\/jats:italic> gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700\u2009bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional <jats:italic>ROBO3<\/jats:italic> variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>, by a review of our in\u2010house database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study has broadened the mutation spectrum of the <jats:italic>ROBO3<\/jats:italic> gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the <jats:italic>ROBO3<\/jats:italic> gene should be included in the local screening strategy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2215","type":"journal-article","created":{"date-parts":[[2023,6,18]],"date-time":"2023-06-18T13:19:48Z","timestamp":1687094388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Early onset horizontal gaze palsy and progressive scoliosis due to a noncanonical splicing\u2010site variant and a missense variant in the <scp><i>ROBO3<\/i><\/scp> gene"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-7701","authenticated-orcid":false,"given":"Sheng","family":"Yi","sequence":"first","affiliation":[{"name":"Genetic and Metabolic Central Laboratory Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Pediatric Diseases Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, Guangxi Key Laboratory of Birth Defects and Stem Cell Biobank, Guangxi Key Laboratory of Birth Defects Research and Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7109-6693","authenticated-orcid":false,"given":"Zailong","family":"Qin","sequence":"additional","affiliation":[{"name":"Genetic and Metabolic Central Laboratory Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Pediatric Diseases Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Guangxi Key Laboratory of Precision Medicine for Genetic Diseases, 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