Sporadic bilateral optic neuropathy in children: The role of mitochondrial abnormalities

Thomas M. Bosley, Michael C Brodsky, Charles M. Glasier, Khaled K. Abu-Amero

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

PURPOSE. To evaluate a group of patients with isolated, early-onset, bilateral optic neuropathy for genetic and biochemical evidence of mitochondrial diseases. METHODS. This case- control study involved 21 patients, 159 control subjects for mitochondrial (mt)DNA sequencing, and 40 control subjects for relative mtDNA content. Patients were identified who had had decreased vision since childhood due to bilateral optic neuropathy characterized by central visual loss with no other major neurologic or ocular abnormality and no clinical evidence of a mitochondrial syndrome. Clinical examination, electroretinograms, and neuroimaging were performed; the entire mtDNA coding region was sequenced in leukocytes of all patients; relative mtDNA content was assessed; and OPA1 and OPA3 nuclear genes associated with dominant and recessive optic atrophy, respectively, were sequenced. Main outcome measures were clinical description, nonsynonymous (NS) mtDNA nucleotide changes, relative mtDNA content, and OPA1 and OPA3 nucleotide changes. RESULTS. Twenty-one unrelated patients (16 male and 5 female; mean age at first examination 13.6 years) had bilateral moderate, relatively symmetric optic neuropathies and normal neurologic examinations other than strabismus in 11 and congenital nystagmus in 9. Four patients had optic nerve hypoplasia. One patient had the nt 11778 primary Leber hereditary optic neuropathy (LHON) mutation, and three others had mtDNA nucleotide changes predicted to be pathologic. The entire group had a small increase (6.7%) in relative mtDNA content of indeterminate statistical significance. No patient had a polymorphism or mutation of OPA1 or OPA3. CONCLUSIONS. A minority of these young patients with sporadic bilateral optic neuropathy had abnormalities of the mitochondrial parameters evaluated. This bilateral optic neuropathy may be due to other genetic, epigenetic, or environmental injury to the optic nerve or to mitochondrial defects not studied.

Original languageEnglish (US)
Pages (from-to)5250-5256
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number12
DOIs
StatePublished - 2008

Fingerprint

Optic Nerve Diseases
Mitochondrial DNA
Nucleotides
Autosomal Dominant Optic Atrophy
Congenital Nystagmus
Eye Abnormalities
Leber's Hereditary Optic Atrophy
Optic Nerve Injuries
Nervous System Malformations
Mitochondrial Diseases
Mutation
Strabismus
Neurologic Examination
Optic Nerve
DNA Sequence Analysis
Epigenomics
Neuroimaging
Case-Control Studies
Molecular Biology
Leukocytes

ASJC Scopus subject areas

  • Medicine(all)
  • Ophthalmology
  • Cellular and Molecular Neuroscience
  • Sensory Systems

Cite this

Sporadic bilateral optic neuropathy in children : The role of mitochondrial abnormalities. / Bosley, Thomas M.; Brodsky, Michael C; Glasier, Charles M.; Abu-Amero, Khaled K.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 12, 2008, p. 5250-5256.

Research output: Contribution to journalArticle

Bosley, Thomas M. ; Brodsky, Michael C ; Glasier, Charles M. ; Abu-Amero, Khaled K. / Sporadic bilateral optic neuropathy in children : The role of mitochondrial abnormalities. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 12. pp. 5250-5256.
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N2 - PURPOSE. To evaluate a group of patients with isolated, early-onset, bilateral optic neuropathy for genetic and biochemical evidence of mitochondrial diseases. METHODS. This case- control study involved 21 patients, 159 control subjects for mitochondrial (mt)DNA sequencing, and 40 control subjects for relative mtDNA content. Patients were identified who had had decreased vision since childhood due to bilateral optic neuropathy characterized by central visual loss with no other major neurologic or ocular abnormality and no clinical evidence of a mitochondrial syndrome. Clinical examination, electroretinograms, and neuroimaging were performed; the entire mtDNA coding region was sequenced in leukocytes of all patients; relative mtDNA content was assessed; and OPA1 and OPA3 nuclear genes associated with dominant and recessive optic atrophy, respectively, were sequenced. Main outcome measures were clinical description, nonsynonymous (NS) mtDNA nucleotide changes, relative mtDNA content, and OPA1 and OPA3 nucleotide changes. RESULTS. Twenty-one unrelated patients (16 male and 5 female; mean age at first examination 13.6 years) had bilateral moderate, relatively symmetric optic neuropathies and normal neurologic examinations other than strabismus in 11 and congenital nystagmus in 9. Four patients had optic nerve hypoplasia. One patient had the nt 11778 primary Leber hereditary optic neuropathy (LHON) mutation, and three others had mtDNA nucleotide changes predicted to be pathologic. The entire group had a small increase (6.7%) in relative mtDNA content of indeterminate statistical significance. No patient had a polymorphism or mutation of OPA1 or OPA3. CONCLUSIONS. A minority of these young patients with sporadic bilateral optic neuropathy had abnormalities of the mitochondrial parameters evaluated. This bilateral optic neuropathy may be due to other genetic, epigenetic, or environmental injury to the optic nerve or to mitochondrial defects not studied.

AB - PURPOSE. To evaluate a group of patients with isolated, early-onset, bilateral optic neuropathy for genetic and biochemical evidence of mitochondrial diseases. METHODS. This case- control study involved 21 patients, 159 control subjects for mitochondrial (mt)DNA sequencing, and 40 control subjects for relative mtDNA content. Patients were identified who had had decreased vision since childhood due to bilateral optic neuropathy characterized by central visual loss with no other major neurologic or ocular abnormality and no clinical evidence of a mitochondrial syndrome. Clinical examination, electroretinograms, and neuroimaging were performed; the entire mtDNA coding region was sequenced in leukocytes of all patients; relative mtDNA content was assessed; and OPA1 and OPA3 nuclear genes associated with dominant and recessive optic atrophy, respectively, were sequenced. Main outcome measures were clinical description, nonsynonymous (NS) mtDNA nucleotide changes, relative mtDNA content, and OPA1 and OPA3 nucleotide changes. RESULTS. Twenty-one unrelated patients (16 male and 5 female; mean age at first examination 13.6 years) had bilateral moderate, relatively symmetric optic neuropathies and normal neurologic examinations other than strabismus in 11 and congenital nystagmus in 9. Four patients had optic nerve hypoplasia. One patient had the nt 11778 primary Leber hereditary optic neuropathy (LHON) mutation, and three others had mtDNA nucleotide changes predicted to be pathologic. The entire group had a small increase (6.7%) in relative mtDNA content of indeterminate statistical significance. No patient had a polymorphism or mutation of OPA1 or OPA3. CONCLUSIONS. A minority of these young patients with sporadic bilateral optic neuropathy had abnormalities of the mitochondrial parameters evaluated. This bilateral optic neuropathy may be due to other genetic, epigenetic, or environmental injury to the optic nerve or to mitochondrial defects not studied.

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