Genetic variation of the mitochondrial complex I subunit NDUFV2 and Parkinson's disease

Abstract

NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), encoding a subunit of mitochondrial complex I, is a candidate gene for several neuronal diseases; schizophrenia, bipolar disorder and Parkinson disease (PD). We screened the entire coding region of NDUFV2 in 33 familial PD patients of North African Arab-Berber ethnicity in which all known genetic forms of PD had been excluded. We detected one novel substitution p.K209R (c.626A>G) in one PD proband. Segregation analysis within the family is inconclusive due to small sample size, but consistent with an autosomal dominant mode of inheritance. Subsequent screening of this mutation in ethnically matched sporadic PD patients (n = 238) and controls (n = 371) identified p.K209R in one additional patient. The clinical features of the mutation carriers revealed a mild form of parkinsonism with a prognosis similar to idiopathic PD. Our findings suggest further studies addressing the role of NDUFV2 variation in PD may be warranted.

Figure 1. Segregation analysis of NDUFV2 p.K209R

A) Males are represented by squares, female by circles, and the probands is arrowed. Individuals diagnosed with Parkinson disease are indicated with black filled symbols, grey filled symbols indicate patients diagnosed with essential tremor. NDUFV2 p.K209R mutation carriers are indicated with mt, non carriers with wt.

Figure 2. Conservation of NDUFV2 p.K209R

Protein homologues were aligned using ClustalW; p.K209R position is highlighted in black, non-conserved amino acid positions are highlighted in grey. GeneBank accession numbers: Homo sapiens, NP_066552; Pan troglodytes, NP_001065254; Macaca mulatta, XP_001099724; Mus musculus, NP_082664; Rattus norvegicus, NP_112326; Canis familiaris, XP_537328; Bos Taurus, NP_776990; Gallus gallus, XP_001232141; Ornithorhynchus anatinus, XP_001507932.