Four Copies of SNCA Responsible for Autosomal Dominant Parkinson’s Disease in Two Italian Siblings

Figure 2

SNCA dosage using CGH-Array and MLPA. (a) MLPA analysis. In these images, normalized peak areas relative to probes considered in MLPA kit P051 (I and III, resp., III;2 and III;3) and P052 (II and IV, resp., III;2 and III;3) are shown. (I and III) The probes related to TNFRSF9 (one probe), PARK7 (twelve probes), and ATP13A2 (two probes) genes are shown in light blue, SNCA (five probes) and two mutation specific probes for p.A30P in SNCA and p.G2019S in LRRK2 genes in brown, LPA (one probe) and PARK2 (twelve probes) genes in dark blue, and the reference probes (eight) in gray. (II and IV) The probes related to genes ATP13A2 (two probes) and UCHL1 (four probes) are shown in light blue, PARK2 (twelve probes), PACRG (one probe), LRRK2 (eight probes), and one mutation specific probe for p.G2019S in LRRK2 in dark blue, SNCA (one probe), CAV1 (one probe), CAV2 (one probe), and GCH1 (five probes) in brown, and the reference probes (nine) in gray. In both patients, an increased ratio in the peak area related to SNCA probes indicates a multiplication at 4q21 chromosomal region. In particular, ratio of SNCA probes in III;2 (SNCA ex2 ratio 1.86, SNCA ex4 ratio 1.81, SNCA ex5 ratio 2.12, SNCA ex6 ratio 1.89, SNCA ex7 ratio 2.08, and SNCA ex3 ratio 1.92) and III;3 (SNCA ex2 ratio 1.92, SNCA ex4 ratio 1.83, SNCA ex5 ratio 1.91, SNCA ex6 ratio 1.95, SNCA ex7 ratio 2.01, and SNCA ex3 ratio 2) suggests the presence of four copies of SNCA locus. (b) Array-CGH profile of chromosome 4 showing a duplication/triplication at 4q21 from 90.013 Mb to 91.26 Mb. Enlargements indicate the duplicated region, and green arrows show the triplicated region. For each analysis, -axis marks the distance along chromosome 4, and -axis marks the hybridization ratio plotted on a log2 scale. Red lines indicate thresholds for clone deletion and green lines for duplication.

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