Neuromelanin MRI in a family with mitochondrial parkinsonism harboring a Y955C mutation in POLG1

Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo 183-0042, Japan.
Parkinsonism & Related Disorders (Impact Factor: 3.97). 05/2013; 19(9). DOI: 10.1016/j.parkreldis.2013.04.011
Source: PubMed


Progressive external ophthalmoplegia (PEO) and parkinsonism can be caused by genetic mutations that affect mitochondrial DNA (mtDNA) maintenance. We characterized parkinsonism in a family with dominantly inherited PEO.

We conducted clinical, histological and genetic analyses on two affected members suffering from PEO and parkinsonism, and reviewed the cases in the literature. To clarify parkinsonism related to multiple mtDNA deletions, we used 3-T neuromelanin magnetic resonance imaging (MRI) to assess signal changes in the substantia nigra (SN) and locus ceruleus (LC) in our patients, and compared the results to those observed in idiopathic Parkinson's disease (iPD) (n = 35).

We report the first case of a Japanese family harboring a heterozygous p.Y955C mutation in POLG1. The clinical features of parkinsonism related to the Y955C mutation in a total of 16 patients, including our two cases, are indistinguishable from iPD. However, neuromelanin MRI showed a distinct pattern in our cases compared to iPD. The neuromelanin imaging results were consistent with the neuropathological findings reported in cases of POLG1 mutations, in which neurons of the SN were profoundly affected while those in the LC were preserved.

Our results suggest that 3-T neuromelanin MRI may be useful for differentiating POLG1 mutation-associated parkinsonism from iPD, and that POLG1 mutations may cause selective neuronal loss in the SN via a mechanism different from that of iPD.

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    • "Interestingly , all of these conditions are considered mitochondrial parkinsonism. The signal intensity changes we observed on neuromelanin imaging in patients with mutations in POLG1 or Parkin provided further evidence that neurons in the SN are profoundly affected while those in the LC are relatively preserved , consistent with the neuropathological findings in each disease (Mukai et al., 2013). In contrast, postmortem neuropathological findings in patients with mutations in alpha-synuclein or LRRK2 showed severe neuronal loss in the LC as well as in the SN, results similar to those in patients with IPD (Poulopoulos et al., 2012). "

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