PMC6497854_01
Representative subcutaneous nodular lesions of the patient. (A) The T1 Weight-sequence showed the subcutaneous nodules on right posterior occipital region with oval and uniform low signal (red arrow) and the new lesion in the brain (blue arrow). (B) The T2 Weight-sequence revealed the nodular skin lesions on right occipital with nearly round low signal and popcorn-like appearance inside (red arrow); (C) the nodular skin lesions on right nasal wing (red arrow).
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Besides, the patient has a 7-year-history of multiple asymptomatic subcutaneous nodules located on right posterior occipital region (Figure 1A-B; red arrow) and the left posterior shoulder. Two years ago, the similar lesions subsequently appeared in the right nasal wing (Figure 1C; red arrow) and the right forehead. T2WI sequence (Figure 1B; red arrow). The color of the overlying skin showed a very slightly bluish hue (Figure 1C) without any redness and swelling. The nodular mass was hard and no tenderness.
Representative cranial MRI of the patient. (A) The T2WI sequence showed the lesions were in round shape (long red arrow) or characterized by mulberry-appearance and a dark rim (short red arrow); (B) some low signal lesions in the diffusion-weighted imaging (DWI)-sequence were characterized by high signals around (red arrows); (C) the susceptibility-weighted imaging (SWI)-sequence (TR:19,TE:25) in 2017 revealed multiple oval or round lesions; (D) the SWI (TR:20,TE:26) in 2018 showed the old lesions in 2017 (Figure 2C; red arrows) had bigger diameters (red arrows) and the new low signal lesions (blue arrows) in the whole brain (cerebral hemispheres, cerebellum, and brain stem). The red box represented the filled veins.
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T2 Weight-sequence (Figure 2A), diffusion-weighted imaging-sequence (Figure 2B) and SWI-sequence in 2017 (Figure 2C) showed multiple abnormally low signals in the brain characterized by mulberry-appearance with a dark rim or oval shape, which were considered as micro-hemorrhagic lesions. The head-MRI SWI sequence from the re-examination at the local hospital in 2018 showed increased microhemorrhagic lesion number (Figure 2D, blue arrows) and extension of the lesion size (Figure 2D, red arrows) at the same position in the brain, involving the cerebral hemispheres, cerebellum, and brain stem. That is the reason why the patient had progressively worsening headaches. Additionally, SWI in 2018 showed the obvious filled veins than before (Figure 2D, red boxes).
Graph showing PDCD10 coding sequence and exon4 sequence analysis. Exons are represented graphically as boxes with the exon number below the boxes, the size of each exon is shown as the number of base pairs directly inside each box. Sequencing with forward primer shows a heterozygous frameshift mutation: the G nucleotide deletion at codon 212 position (red circle). The frameshift mutation (c.212delG) led to premature protein termination.
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It is a frameshift mutation in the heterozygous state: the G nucleotide deletion at codon 212 position (Figure 3).
PDCD10 Tertiary structure alteration prediction by RaptorX tool. (A) Tertiary structure of wild-type protein. (B) Tertiary structure of p.S71Tfs*18 affected protein.
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Effects of the novel mutation on PDCD10 tertiary structure were predicted by RaptorX prediction tool The results reveal tertiary structure change in mutated protein (Figure 4B) compared to wild-type one (Figure 4A).