Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted TATA-box of human PMP22 promoter to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multiple copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a proof-of-concept that CRISPR/Cas9-mediated targeting of TATA-box can be utilized to treat CMT1A.
Background/Aims: The miss rate of colon polyps and its related factors have not been clearly identified yet. This study aims to review the miss rate of polyps both on the patient-level and on the polyp-level and to analyze the factors affecting the miss rate such as those related to the endoscopist, procedure, patient, and polyp. Methods: From August 2011 to August 2013, patients who underwent elective second colonoscopy for resection of polyps, the sizes of which were not small enough to be resected by biopsy forceps alone at first colonoscopy, were enrolled retrospectively. Results: The miss rate on the patient-level was 59.2% (234/395) and on the polyp-level was 27.9% (578/2,068). There was no significant difference in the miss rate depending on the experience of the endoscopists or characteristics of the patients. In terms of the procedure, the miss rate was higher when the colonoscopy was performed in the afternoon (OR 1.632, p=0.046). It was found that the miss rate of polyps increased when the polyps were small (OR 4.595, p<0.001 in <5 mm/OR 3.447, p<0.001 in 5-10 mm), flat or sessile (OR 2.406, p<0.001 in flat/OR 1.768, p=0.002 in sessile), and located in the left colon (OR 1.391, p=0.007). Conclusions: The experience of endoscopists did not have influence on the accuracy of polyp detection. However, the fatigue of endoscopists in the afternoon is considered to render polyp detection less accurate. Also, the large curves and folds of the sigmoid colon are regarded as a reason for the higher miss rate of polyps in the left colon. (Korean J Gastroenterol 2014;64:24-30)
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