Horizontal Gaze Palsy with Progressive Scoliosis is a rare, congenital autosomal recessive disorder caused by mutations in the ROBO3 gene. It is characterized by the absence of conjugate horizontal eye movements with preserved vertical gaze, variable convergence, and progressive scoliosis, developing in childhood and adolescence. ROBO3 gene mutations are causative of the lack, or at least reduction, of crossing of the descending corticospinal and ascending lemniscal sensory tracts in the medulla. To date, 39 different mutations, including missense, nonsense, frameshift, and splice site mutations have been described in the ROBO3 gene and related to Horizontal Gaze Palsy With Progressive Scoliosis. In addition, a lot of variants of uncertain pathological significance have been reported for the first time by Illumina Clinical Services. Here we report an update on mutations of the ROBO3 gene and some information on the pathogenesis but much remains to be investigated on the consequences of mutations on ROBO3 expression and function. Therefore, further detailed functional analyses are necessary to clarify a possible role of the variants of uncertain pathological significance as the cause of the disease. In conclusion, we hope that this article will help in molecular screening for the ROBO3 gene and will contribute to enlargement of the ROBO3 gene variation database.
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