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.

dx.doi.org/10.1001/archneur.64.6.890, hdl.handle.net/1765/35388
Archives of Neurology
Erasmus MC: University Medical Center Rotterdam

Spruijt, L, Smeets, H.J.M, Hendrickx, A, Bettink-Remeijer, M.W, Maat-Kievit, A.A, Schoonderwoerd, K, … Hintzen, R.Q. (2007). A MELAS-associated ND1 mutation causing Leber hereditary optic neuropathy and spastic dystonia. Archives of Neurology, 64(6), 890–893. doi:10.1001/archneur.64.6.890