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Liesbeth Spruijt, MD; Hubert J. Smeets, PhD; Alexandra Hendrickx, BApplSc; Marijke Wefers Bettink-Remeijer, MD; A. Maat-Kievit, MD, PhD; Kees C. Schoonderwoerd, PhD; Wim Sluiter, PhD; Ireneaus F. de Coo, MD, PhD; Rogier Q. Hintzen, MD, PhD

Arch Neurol. 2007;64(6):890-893.

Objective  To report a novel mutation that is associated with Leber hereditary optic neuropathy (LHON) within the same family affected by spastic dystonia.

Design  Leber hereditary optic neuropathy is a mitochondrial disorder characterized by isolated central visual loss. Of patients with LHON, 95% carry a mutation in 1 of 3 mitochondrial DNA–encoded complex I genes. The complete mitochondrial DNA was screened for mutations in a patient with LHON without 1 of these 3 primary mutations. The heteroplasmy level and biochemical consequence of the mutation were determined.

Results  A pathogenic 3697G>A/ND1 mutation was detected and seemed associated with an isolated complex I deficiency. This family has similar clinical characteristics as the previously described families with LHON and dystonia with an ND6 mutation.

Conclusions  The 3697G>A/ND1 mitochondrial DNA mutation causes the LHON and spastic dystonia phenotype in the same family. This mutation can also cause MELAS syndrome (which encompasses mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke), and other genetic factors may contribute to the clinical expression.

Author Affiliations: Department of Genetics and Cell Biology (Drs Spruijt and Smeets and Ms Hendrickx) and Research Institute Growth and Development (Dr Smeets), University of Maastricht, Maastricht; Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen (Dr Spruijt); The Rotterdam Eye Hospital (Dr Bettink-Remeijer) and Departments of Clinical Genetics (Dr Maat-Kievit), Biochemistry (Drs Schoonderwoerd and Sluiter), and Neurology (Drs de Coo and Hintzen), Erasmus MC, Rotterdam, the Netherlands.

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