PMC6712964_01
(A) Pedigree of the family. (B) Electropherograms of the mutation c.991G>T and c.1427 + 1G>A. (C) Schematic of PLA2G6 gene (NM_003560.2) and locations of mutations. (D) Conservation of amino acid residue across different species in PLA2G6 gene. (E) The 3-D structures of wild type and mutant-type proteins.
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F1
There was no history of parkinsonism and related disease in his previous generations, and his parents were not consanguineous marriage (Figure 1A). A compound heterozygous mutation c.991G>T/c.1472+1G>A was detected in the patient (Figure 1B). The c.991G>T mutation is located in exon 7 of the NM_003560 transcript (Figure 1C), which causes a p.331D>Y transition and leads to aspartic acid-tyrosine change in the seventh ankyrin repeats (ranging from amino acid 150 to 382) (Figure 1E). The number 331 aspartic acid is highly conserved across different species (Figure 1D). The c.1472+1G>A mutation is located in the junction between exon 10 and intron 10, acts as a splice donor variant affecting its splicing (Figure 1C).
Brain MRI examination of the patient and controls. (A) SWI image shows substantia nigra and red nucleus. Hyperintensity is found in substantia nigra of patient's mother and healthy controls (yellow arrow), but not in this patient. (B) SWI image shows basal ganglia. Hypointensity can be seen in globus pallidus and margin of putamen in all subjects. (C,D) MP2RAGE sagittal image shows deepened cerebellar fissures in this patient (red arrow). (E) Fiber tracking shows sparser tract in the patient (red arrow).
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SWI images showed that the patient presented the absence of bilateral nigrosome-1 hyperintensity, also known as "swallow tail sign," while it was presented in patient's mother and healthy controls (Figure 2A). Hypointense signals in bilateral globus pallidus and margin of putamen were found in all subjects (Figure 2B). MP2RAGE structural images also showed cerebellar atrophy in the patient as compared with his mother and three age-matched healthy controls (Figures 2C,D). The cerebellar white matter fiber tracts from this patient was sparser than controls, providing more evidence of cerebellar atrophy (Figure 2E).