AUTHOR=Huang Lijuan , Guo Jianlin , Xie Yan , Zhou Yunyu , Wu Xiaofei , Li Hui , Peng Yun , Li Ningdong 

TITLE=Clinical features and genotypes of six patients from four families with horizontal gaze palsy with progressive scoliosis

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.949565

DOI=10.3389/fped.2022.949565

ISSN=2296-2360

ABSTRACT=<sec><title>Background</title><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 (<italic>ROBO3</italic>) gene mutation. This study aimed to describe the clinical features of six patients with HGPPS and investigate the corresponding <italic>ROBO3</italic> gene mutations.</p></sec><sec><title>Methods</title><p>Patients underwent detailed clinical and imaging examinations. Whole-exome sequencing was performed to detect nucleotide variations in the disease-causing genes of HGPPS.</p></sec><sec><title>Results</title><p>Six pathogenic variants were detected in the <italic>ROBO3</italic> gene from six patients with HGPPS, including two novel compound heterozygous mutations, c.1447C &gt; T (p.R483X) and c.2462G &gt; C (p.R821P); c.1033G &gt; C (p.V345L) and c.3287G &gt; T (p.C1096F); a novel homozygous indel mutation, c.565dupC (p.R191Pfs*61); and a known missense mutation, c.416G &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.</p></sec><sec><title>Conclusion</title><p>Our genetic findings will expand the spectrum of <italic>ROBO3</italic> mutations and help inform future research on the molecular mechanism of HGPPS.</p></sec>