{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:30:20Z","timestamp":1773379820265,"version":"3.50.1"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare disorder mainly involved in ocular movement and spinal development. It is caused by a roundabout guidance receptor 3 (<jats:italic>ROBO3<\/jats:italic>) gene mutation. This study aimed to describe the clinical features of six patients with HGPPS and investigate the corresponding <jats:italic>ROBO3<\/jats:italic> gene mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients underwent detailed clinical and imaging examinations. Whole-exome sequencing was performed to detect nucleotide variations in the disease-causing genes of HGPPS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six pathogenic variants were detected in the <jats:italic>ROBO3<\/jats:italic> gene from six patients with HGPPS, including two novel compound heterozygous mutations, c.1447C &amp;gt; T (p.R483X) and c.2462G &amp;gt; C (p.R821P); c.1033G &amp;gt; C (p.V345L) and c.3287G &amp;gt; T (p.C1096F); a novel homozygous indel mutation, c.565dupC (p.R191Pfs*61); and a known missense mutation, c.416G &amp;gt; T (p.G139V). Patients with HGPPS had horizontal conjugated eye movement defects and scoliosis with variable degrees, as well as flattened pontine tegmentum and uncrossed corticospinal tracts on magnetic resonance imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our genetic findings will expand the spectrum of <jats:italic>ROBO3<\/jats:italic> mutations and help inform future research on the molecular mechanism of HGPPS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.949565","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T05:35:52Z","timestamp":1663133752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical features and genotypes of six patients from four families with horizontal gaze palsy with progressive 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