Purpose: To describe a family with horizontal gaze palsy and progressive scoliosis with a deleterious mutation in the ROBO3 gene.
Methods: All family members had full ophthalmologic, neurologic, and orthopedic examinations and complete sequencing of the ROBO3 gene.
Results: Four affected members had complete loss of horizontal gaze with progressive scoliosis that varied between family members. ROBO3 sequencing revealed a novel 15 base deletion (c.2_16 delTGCTGCGCTACCTGC) in exon 1 that segregated in homozygous form with the phenotype and probably alters the shape and ionic charge of the extracellular immunoglobulin motif 1. This mutation was not detected in 100 control chromosomes.
Conclusions: The novel ROBO3 mutation in this family may be among the most deleterious yet reported. Family members in general were severely affected, but comparison of this family to other families with ROBO3 mutations did not yield a definitive phenotype-genotype correlation.