Introducing and Reviewing a Novel Mutation of ROBO3 in Horizontal Gaze Palsy with Progressive Scoliosis from a Chinese Family.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disorder caused by ROBO3 gene mutations. To date, the number of confirmed HGPPS cases caused by gene mutations is estimated at 76. However, HGPPS caused by ROBO3 gene mutation has not been reported in the Chinese population. In this study, the clinical data, brain imaging features, somatosensory evoked potentials (SEP), and ROBO3 gene mutations were obtained for two Chinese patients with HGPPS. The proband was an 11-year-old boy. He developed horizontal eye movement disorder at the age of 1 year and scoliosis at the age of 11 years. Two eyeballs fixed in the midline position were revealed by neurological examination. A dorsal cleft in the pons and a butterfly-shaped medulla were shown by brain magnetic resonance imaging. Again, most corticospinal bundles did not cross in the brainstem, as revealed by diffusion tensor imaging. SEP confirmed that most somatosensory projections were uncrossed. The proband's 7-year-old brother exhibited similar clinical manifestations and imaging features. The brothers had compound heterozygous mutations c.3165G>A (p.W1055X) and c.955G>A (p.E319K) of the ROBO3 gene. The c.3165G>A mutation is a novel nonsense mutation that has not been previously reported. This study reports the first two cases of HGPPS carrying a novel ROBO3 gene mutation in patients from a Chinese family, thereby expanding the disease spectrum. Reports from the literature show that missense mutation is the most common mutational type in the ROBO3 gene. Early ROBO3 gene detection is required for patients exhibiting early-onset eyeball movement disorder to confirm HGPPS disease.