title: Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations.
abstract: BACKGROUND
  To describe clinical and genetic observations in a patient with horizontal gaze palsy and progressive scoliosis (HGPPS) without identified mutations in the ROBO3 gene.
  
  
  METHODS
  Neurologic and orthopedic evaluation of the proband; sequencing all exons, exon-intron boundaries, and promoter region of ROBO3 in the proband and his mother. Array CGH was also carried out in the proband and his mother to evaluate possible chromosomal deletion(s) and/or duplication(s).
  
  
  RESULTS
  The proband had complete horizontal gaze restriction with full vertical gaze and small amplitude horizontal pendular nystagmus. He also had severe scoliosis and brainstem hypoplasia pathognomonic of HGPPS. However, complete sequencing of ROBO3 twice in both forward and reverse directions did not reveal any mutations. Array CGH investigation revealed no chromosomal abnormalities.
  
  
  CONCLUSIONS
  This patient had clinical and neuroimaging characteristics considered pathognomonic of HGPPS and yet did not have ROBO3 mutations. A clinical misdiagnosis is unlikely in the absence of facial weakness (typical of Moebius syndrome), deafness (typical of the HOXA1 spectrum), or mental retardation (typical of other central decussation abnormalities). It is perhaps more likely that a phenotype identical to HGPPS can be caused by abnormalities in ROBO3 splice variant expression, by mutations of a gene other than ROBO3, or by some environmental or epigenetic factor(s) inhibiting the action of ROBO3 or its protein product in the developing brainstem.
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuamero@gmail.com
authors.forename: Khaled K
authors.initials: KK
authors.lastname: Abu-Amero
authors.forename: Flavio
authors.initials: F
authors.lastname: Faletra
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.forename: Fulvio
authors.initials: F
authors.lastname: Parentin
authors.forename: Stefano
authors.initials: S
authors.lastname: Pensiero
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Alorainy
authors.forename: Ali M
authors.initials: AM
authors.lastname: Hellani
authors.forename: Dario
authors.initials: D
authors.lastname: Catalano
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bosley
mesh_terms: D002648:Child; D006801:Humans; D007738:Kyphosis / Q000175:diagnosis / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000209:etiology*; D015840:Oculomotor Nerve Diseases / Q000175:diagnosis / Q000209:etiology*; D010375:Pedigree; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics*; D012600:Scoliosis / Q000175:diagnosis / Q000209:etiology*; D000097905:Roundabout Proteins
chemical_list: D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C499630:ROBO3 protein, human; D000097905:Roundabout Proteins