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. 2009 Jan;65(1):19-23.
doi: 10.1002/ana.21415.

Characterization of PLA2G6 as a locus for dystonia-parkinsonism

Coro Paisan-Ruiz  1 , Kailash P Bhatia, Abi Li, Dena Hernandez, Mary Davis, Nick W Wood, John Hardy, Henry Houlden, Andrew Singleton, Susanne A Schneider
Affiliations

Characterization of PLA2G6 as a locus for dystonia-parkinsonism

Coro Paisan-Ruiz et al. Ann Neurol. 2009 Jan.

Abstract

Background: Although many recessive loci causing parkinsonism dystonia have been identified, these do not explain all cases of the disorder.

Methods: We used homozygosity mapping and mutational analysis in three individuals from two unrelated families who presented with adult-onset levodopa-responsive dystonia-parkinsonism, pyramidal signs and cognitive/psychiatric features, and cerebral and cerebellar atrophy on magnetic resonance imaging but absent iron in the basal ganglia.

Results: We identified areas of homozygosity on chromosome 22 and, subsequently, PLA2G6 mutations.

Interpretation: PLA2G6 mutations are associated with infantile neuroaxonal dystrophy and have been reported previously to cause early cerebellar signs, and the syndrome was classified as neurodegeneration with brain iron accumulation (type 2). Our cases have neither of these previously pathognomic features. Thus, mutations in PLA2G6 should additionally be considered in patients with adult-onset dystonia-parkinsonism even with absent iron on brain imaging.

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Conflict of interest statement

None of the authors has stated any conflict of interest.

Figures

Figure 1:
Figure 1:
(A) Pedigree of family 1 (p.R741Q mutation) showing the segregation. (B) Pedigree of family 2 (p.R747W mutation). Full symbols represent affected individuals, empty symbols unaffected family members. Diamond-shaped symbols indicate (unaffected) individuals of unspecified gender. #, further siblings. The index cases are highlighted by an arrow. Double lines indicate consanguineous marriages between first cousins. +/+, mutant; −/+, carrier; −/−, wild type; Neither mutation variant was found in 226 control individuals of ethnic Indian/Pakistani origin.
Figure 2:
Figure 2:
Bain MRI of patients 1 (A) and 2 (B). A) There is no evidence of iron accumulation in the basal ganglia (T2 *-weighted image, (left)). There are white matter increased signal changes, mainly around the frontal horn (T2 FLAIR (top right, long arrow). There is progressive generalized volume loss. Cerebellar volume is normal (T1-weighted image (bottom right, short arrow)). B) There is no iron deposition in the basal ganglia on T2*-weighted imaging (left). A normal MRI study, apart from mild cerebral atrophy (T1-weighted slides, (right)).
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