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BACKGROUND AND OBJECTIVE: Alexander disease (ALXDRD) is an autosomal dominant neurologic disorder caused by mutations in the glial fibrillary acidic protein (GFAP) gene and is pathologically defined by Rosenthal fiber accumulation. Most mutations are exonic missense mutations, and splice site mutations are rare. We report a very-late-onset autopsied case of adult-onset ALXDRD with a novel splice site mutation. METHODS: Genetic testing of GFAP was performed by Sanger sequencing. Using autopsied brain tissues, GFAP transcript analysis was performed. RESULTS: The patient presented mild upper motor neuron symptoms in contrast to the severe atrophy of spinal cord and medulla oblongata. The patient had c.619-1G>A mutation, which is located in the canonical splice acceptor site of intron 3. The brain RNA analysis identified the r.619_621del (p.Glu207del) mutation, which is explained by the activation of the cryptic splice acceptor site in the second and third nucleotides from the 5' end of the exon 4. DISCUSSION: GFAP gene expression analysis is necessary to clarify the effects of intronic mutations on splicing, even if they are in canonical splice sites. This case showed a much milder phenotype than those in previous cases with missense mutations at Glu207, thereby expanding the clinical spectrum of ALXDRD with Glu207 mutation.
RESUMO
Objective Gastric endoscopic submucosal dissection (ESD) is currently a standard procedure, and proton pump inhibitors (PPIs) are most commonly used to treat post-ESD ulcers. Vonoprazan, a potassium-competitive acid blocker (P-CAB), reportedly inhibits gastric acid secretions more effectively than PPIs. Combination therapy of a PPI plus rebamipide is effective for treating larger ulcers. Our goal was to evaluate the effects of vonoprazan plus rebamipide compared to esomeprazole plus rebamipide for the treatment of post-ESD ulcers. Methods First, vonoprazan plus rebamipide (V group) or esomeprazole plus rebamipide (E group) was orally administered to subjects for eight weeks. We then evaluated the ulcer healing process at four and eight weeks after the procedure using a gastric ulcer stage system and by measuring the ulcer size. Patients A total of 84 patients who underwent ESD for gastric neoplasms between September 2015 and December 2017 in Tsuchiura Kyodo General Hospital were included in this randomized controlled trial. Results The ulcer scar rates at week 4 in the V group (n=43) and E groups (n=39) were 20.9% and 15.4%, while those at week 8 were 90.7% and 92.3%, respectively. The ulcer reduction rates at week 4 in the V and E groups were 94.6% and 93.8%, and those at week 8 were 99.7% and 99.3%, respectively. The ulcer scar rates and reduction rates were not significantly different between the two groups. Conclusion Combination therapy consisting of vonoprazan plus rebamipide was not superior to that of esomeprazole plus rebamipide for post-ESD ulcer healing (UMIN000019516).