Partial chromosome 7 duplication with a phenotype mimicking the HOXA1 spectrum disorder

Khaled K. Abu-Amero, Altaf A. Kondkar, Mustafa A.M. Salih, Ibrahim A. Alorainy, Arif O. Khan, Darren T. Oystreck, Thomas M. Bosley

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Purpose: 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.

Original languageEnglish (US)
Pages (from-to)90-96
Number of pages7
JournalOphthalmic genetics
Issue number1-2
StatePublished - Mar 1 2013
Externally publishedYes


  • Array comparative genomic hybridization
  • Congenital hearing impairment
  • Duane retraction syndrome
  • HOXA1 spectrum
  • Mental retardation
  • Seizures

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Ophthalmology
  • Genetics(clinical)


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