case_images: PMC11774911_01
case_images: Brain CT taken at 2 years and 4 months old, and 2 weeks after disease onset: multiple spotty and patchy low-density lesions in the bilateral basal ganglia and thalamus.
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case_images: F1
case_images: Brain computed tomography (CT) showed multiple spotty and patchy low-density lesions in bilateral basal ganglia and thalamus (Figure 1).
case_images: Brain MRI A1-6: at 2 years and 4 months of age (2 weeks of disease duration after disease onset): T2WI, T2-FLAIR, DWI high, and T1WI low signals in the right putamen and brainstem; T2WI, T2-FLAIR, and T1WI low signals in the bilateral thalamus and basal ganglia. B1-6: at 2 years and 5 months old (1.5 months after disease onset): T2, T2-FLAIR high signals in the right putamen and right brainstem disappeared.
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case_images: F2
case_images: T2-FLAIR (Fluid attenuated inversion recovery) and DWI (Diffusion-weighted imaging). The bilateral basal ganglia and thalamus were patchy with low signal on T1, low signal on T2-FLAIR, and DWI (Figure 2). MRI showed that the lesions had improved (Figure 2). Muscle strength in the left limb recovered to grade IV.
case_images: The Sanger sequencing of the patient's family. The patint had compound heterozygous variants in ADA2 gene, NM_017424 c.1358A>G p. (Tyr453Cys)and c.1082-7T>A. The variant NM_017424 c.1082-7T>A was found in both the patient and her mother (A). The variant NM_017424 c.1358A>G p. (Tyr453Cys) was found in both the patient and her father (B).
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case_images: PMC11774911_01_fgene-15-1478581-g003.jpg
case_images: F3
case_images: The compound heterozygous variants in the ADA2 gene were identified through the trio-WES and Sanger sequencing (Figure 3). Variant 1 is c.1082-7T>A (Figure 3A): This intron variation had not been recorded in gnomAD (version 4.1.0), 1,000 genome Project, dbSNP or Clinvar Database (PM2_Supporting). Variant 2 is c.1358A>G (Figure 3B): this missense variant was a pathogenic variant which has been reported in previous literature and recorded in Clinvar Database (PM3_Very strong).
case_images: The mRNA reverse transcription-Sanger sequencing in the variant c.1082-7T>A. The cDNA sequence 1 of the patient showed the variant c.1082-7T>A, which led to 21 nucleotides deletion in the exon6, exon 7 junction site, compared with the cDNA sequence 2 (A). The cDNA sequence 1 of mother showed the variant c.1082-7T>A, which leaded to 21 nucleotides deletion in the exon6, exon 7 junction site, compared with the cDNA sequence 2 (B). The cDNA sequence of father showed the normal result (C). The variant c.1082-7T>A was finally confirmed with the affect on mRNA splicing. It lead to 21 nucleotides deletion in the exon6, exon 7 junction site, resulting, finally resulting protein truncation Leu362Glnfs*45 (D).
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case_images: F4
case_images: The deletion was locadted in the exon 6, exon 7 junction site (Figure 4).
case_images: The test of ADA2 enzymatic activity of the patient. Compared with the wild type individuals, the patient's ADA2 enzyme activity showed a significnat decrease. The ADA2 enzyme activity was 0 (Normal value range >0.003 mg/L).
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case_images: F5
case_images: The specific results are shown in Figure 5.