Novel sequence variants detected in this study.

<p>Key: Heterozygous, Het; Homozygous, Homo; Familial, FM; Sporadic, SP; Not available, n.a.</p><p>* Frequency: No. of control carriers/ total No. of controls.</p><p>Novel sequence variants detected in this study.</p

Genetic characterization of <i>PARKIN</i> (p.G409R) and <i>PINK1</i> (p.E195Q) variants and their predicted functional impact.

<p>(A) Pedigree of FM 49 with LOPD. (B) Part of the sequencing chromatogram of <i>PINK1</i> exon 6 showing homozygous c.1225G>A mutation (corresponding to p.G409R substitution) in 49-a and 49-b but not in WT. (C) Part of the sequencing chromatogram of <i>PARKIN</i> exon 5 showing heterozygous c.583G>C variant (corresponding to p.E195Q substitution) in SP-7. (D) Ribbon presentation of PINK1^WT and PINK1^mut structural models. The secondary structures are colored as follows: β-strands (magenta), α-helices (cyan), coils (light pink). (E) PINK1^WT. (F) PINK1^mut. The spatial distance between the P+1 binding motif (cyan) and helix G (blue), measured in Angstrom (Å), is increased in PINK1^mut compared to PINK1^WT. A close-up view of the activation loop (aa 384–417) containing the P+1 binding motif and the helix G is represented [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135950#pone.0135950.ref027" target="_blank">27</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135950#pone.0135950.ref028" target="_blank">28</a>]. (G and H) p.E195Q has a very subtle impact on the protein conformation. Ribbon presentation of PARKIN^WT and PARKIN^mut structural models. The UPD, is shown in (yellow) or (cyan) in PARKIN^WT and PARKIN^mut, respectively. (G) Positions of the missing β-strand and α-helix are indicated by the asterisk and the hash symbols, respectively. (H) Superimposition of PARKIN^WT and PARKIN^mut showing parts of the protein (indicated by a hash symbol) that had lost the β-strand structure and adopted a random coil instead. Age at onset: AAO. Years: y. WT: wild-type.</p