Novel POLG splice site mutation and optic atrophy

Margherita Milone, Jing Wang, Teerin Liewluck, Li Chieh Chen, Jacqueline A. Leavitt, Lee Jun Wong

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: To investigate the molecular etiology of 2 unrelated patients with a multisystem mitochondrial disorder accompanied by optic atrophy in one of them. Design: Clinical examination and neurophysiological, radiological, morphological, and molecular analyses. Setting: Tertiary care neuromuscular clinic and molecular genetics laboratory. Patients: A 65-year-old man (patient 1) with dyschromatopsia and vision loss since childhood developed progressive external ophthalmoplegia, ptosis, and myopathy in the seventh decade of life and was found to have optic atrophy. A 63-year-old man (patient 2) with a similar phenotype, without visual symptoms, experienced also hearing loss and parkinsonism. Main Outcome Measures: Description of the clinical and molecular findings. Results: A muscle biopsy specimen showed ragged-red, ragged-blue, and cytochrome c oxidase-negative fibers in both patients. Because optic atrophy in patient 1 suggested an autosomal dominant OPA1-related disorder, the OPA1 gene was first sequenced, the results of which did not detect any mutations. Southern blot and polymerase chain reaction analyses of muscle mitochondrial DNA revealed multiple deletions. Sequencing of POLG detected a novel variant, c.3104+3A>T, in both patients. Patient 1 was compound heterozygous for a known p.F749S mutation; patient 2 had p.G848S as the second mutation. Analysis of POLG complementary DNA showed that c.3104+3A>T results in skipping of exon 18. Conclusion: Early-onset dyschromatopsia and optic atrophy can occur not only in OPA1-related but also in POLG-related disorders with significant impact on genetic counseling.

Original languageEnglish (US)
Pages (from-to)806-811
Number of pages6
JournalArchives of Neurology
Volume68
Issue number6
DOIs
StatePublished - Jun 2011

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Optic Atrophy
Mutation
Chronic Progressive External Ophthalmoplegia
Optics
Mitochondrial Diseases
Muscles
Genetic Counseling
Parkinsonian Disorders
Muscular Diseases
Electron Transport Complex IV
Tertiary Healthcare
Southern Blotting
Mitochondrial DNA
Hearing Loss
Molecular Biology
Exons
Complementary DNA
Outcome Assessment (Health Care)
Phenotype
Biopsy

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Milone, M., Wang, J., Liewluck, T., Chen, L. C., Leavitt, J. A., & Wong, L. J. (2011). Novel POLG splice site mutation and optic atrophy. Archives of Neurology, 68(6), 806-811. https://doi.org/10.1001/archneurol.2011.124

Novel POLG splice site mutation and optic atrophy. / Milone, Margherita; Wang, Jing; Liewluck, Teerin; Chen, Li Chieh; Leavitt, Jacqueline A.; Wong, Lee Jun.

In: Archives of Neurology, Vol. 68, No. 6, 06.2011, p. 806-811.

Research output: Contribution to journalArticle

Milone, M, Wang, J, Liewluck, T, Chen, LC, Leavitt, JA & Wong, LJ 2011, 'Novel POLG splice site mutation and optic atrophy', Archives of Neurology, vol. 68, no. 6, pp. 806-811. https://doi.org/10.1001/archneurol.2011.124
Milone, Margherita ; Wang, Jing ; Liewluck, Teerin ; Chen, Li Chieh ; Leavitt, Jacqueline A. ; Wong, Lee Jun. / Novel POLG splice site mutation and optic atrophy. In: Archives of Neurology. 2011 ; Vol. 68, No. 6. pp. 806-811.
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