case_images: PMC11752879_01
case_images: Diffuse, faint high signal on fluid-attenuated inversion recovery is observed in the deep white matter on head magnetic resonance imaging (yellow arrow). No apparent signs of meningitis, tumorous lesions, abnormal signals or enhancement, pathological ventricular enlargement, or brainstem atrophy are noted.
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case_images: MRI showed no infarction, and magnetic resonance angiography did not reveal any considerable stenosis or aneurysms ( Figure 1 ). MRI of the cervical, thoracic, and lumbar spines revealed no substantial abnormalities.
case_images: Result of the TNFAIP3 gene variant function analysis. To confirm whether the patient had a disease-related variant in the TNFAIP3 gene, we conducted functional analysis of variants of the same gene using a previously reported method. The Dual-Luciferase Reporter Assay System (Promega) was used to perform a reporter gene assay that examines nuclear factor kappa B (NF-kappaB) expression in response to tumor necrosis factor stimulation. For the variant observed in this case as R87X on the right end, compared with the wild type, the Luciferase activity is higher, indicating a substantial failure of NF-kappaB activity inhibition, confirming it as a pathological variant. Mock: A20 haploinsufficiency (A20)-deficient human embryonic kidney (HEK) 293 cells were transfected with 10 ng of pcDNA3.1+ mock vector per well. Wild-type: A20-deficient HEK293 cells were transfected with 10 ng of pcDNA3.1+ myc-A20 wild-type per well. F127C: TNFAIP3 gene single nucleotide polymorphisms as the negative variant control. W85fs: TNFAIP3 gene frameshift variant as the pathogenic variant control. R87X: TNFAIP3 gene c.159C>T variant (present case).
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case_images: To confirm whether the TNFAIP3 variant was disease-related, we performed variant functional analysis of the gene using a previously reported method ( Figure 2 ).
case_images: (A) In addition to the proband (II-3), his elder sister (II-2), niece (III-1), and daughter (III-3) exhibit symptoms of oral ulcers suggestive of A20 haploinsufficiency. (B) Patient's clinical course after visiting our hospital. WBC, white blood cell; CRP, C-reactive protein.
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case_images: His relatives, namely his elder sister (II-2), niece (III-1), and daughter (III-3), besides the index case (II-3), exhibited symptoms suggestive of HA20 with oral ulceration ( Figure 3A ). Colchicine was discontinued owing to diarrhea, and tapering of prednisolone to a dosage of 2 mg/day became possible ( Figure 3B ).