title: Partial chromosome 7 duplication with a phenotype mimicking the HOXA1 spectrum disorder.
abstract: OBJECTIVE
  To evaluate possible monogenic and chromosomal anomalies in a patient with bilateral Duane retraction syndrome and hearing impairment resulting in a phenotype resembling the HOXA1 spectrum disorder.
  
  
  METHODS
  Sequencing HOXA1 and performing high resolution array comparative genomic hybridization (arrayCGH).
  
  
  RESULTS
  The proband had bilateral Duane retraction syndrome (DRS) with severe hearing loss bilaterally and an absent right vertebral artery, mimicking the major features of the Bosley-Salih-Alorainy variant of the HOXA1 spectrum. However, he also had developmental delay, mild mental retardation, and seizures. His parents were not related, but his father had milder sensorineural hearing loss bilaterally, and two paternal uncles and a paternal cousin had seizures. Neuroimaging revealed moderate maldevelopment of inner ear bony anatomy bilaterally. HOXA1 sequencing was normal, but arrayCGH revealed a small partial duplication of chromosome 7 encompassing only the PTPRN2 gene (protein tyrosine phosphatase, receptor type, N polypeptide 2) that was not present in his parents, an unaffected brother, or 53 normal ethnically-matched individuals.
  
  
  CONCLUSIONS
  PTPRN2 is not yet linked to a genetic syndrome, although its expression has been identified in the adult human brain, in certain tumors, and in association with type 1 diabetes mellitus. The phenotype of this patient is strikingly similar to, but not identical to, that of the HOXA1 spectrum disorder. The findings in this patient raise the possibility that PTPRN2 may be active during early development of the human brainstem and that its overexpression may cause bilateral DRS with hearing loss as occurs in patients with homozygous HOXA1 mutations.
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: Altaf A
authors.initials: AA
authors.lastname: Kondkar
authors.forename: Mustafa A M
authors.initials: MA
authors.lastname: Salih
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Alorainy
authors.forename: Arif O
authors.initials: AO
authors.lastname: Khan
authors.forename: Darren T
authors.initials: DT
authors.lastname: Oystreck
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bosley
mesh_terms: D001324:Autoantigens / Q000235:genetics; D001933:Brain Stem / Q000002:abnormalities; D002648:Child; D058674:Chromosome Duplication / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D003937:Diagnosis, Differential; D004370:Duane Retraction Syndrome / Q000175:diagnosis* / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009421:Nervous System Malformations / Q000175:diagnosis* / Q000235:genetics; D015835:Ocular Motility Disorders / Q000175:diagnosis* / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000099261:Homeobox A1 Protein
chemical_list: D001324:Autoantigens; D018398:Homeodomain Proteins; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D014157:Transcription Factors; D000099261:Homeobox A1 Protein; C102889:PTPRN2 protein, human