Abstract
Background
At least 50% of patients with suspected Mendelian disorders remain undiagnosed after whole-exome sequencing (WES), and the extent to which non-coding variants that are not ...captured by WES contribute to this fraction is unclear. Whole transcriptome sequencing is a promising supplement to WES, although empirical data on the contribution of RNA analysis to the diagnosis of Mendelian diseases on a large scale are scarce.
Results
Here, we describe our experience with transcript-deleterious variants (TDVs) based on a cohort of 5647 families with suspected Mendelian diseases. We first interrogate all families for which the respective Mendelian phenotype could be mapped to a single locus to obtain an unbiased estimate of the contribution of TDVs at 18.9%. We examine the entire cohort and find that TDVs account for 15% of all “solved” cases. We compare the results of RT-PCR to in silico prediction. Definitive results from RT-PCR are obtained from blood-derived RNA for the overwhelming majority of variants (84.1%), and only a small minority (2.6%) fail analysis on all available RNA sources (blood-, skin fibroblast-, and urine renal epithelial cells-derived), which has important implications for the clinical application of RNA-seq. We also show that RNA analysis can establish the diagnosis in 13.5% of 155 patients who had received “negative” clinical WES reports. Finally, our data suggest a role for TDVs in modulating penetrance even in otherwise highly penetrant Mendelian disorders.
Conclusions
Our results provide much needed empirical data for the impending implementation of diagnostic RNA-seq in conjunction with genome sequencing.
To evaluate the demographic data and complications in children who had undergone percutaneous endoscopic gastrostomy (PEG) over 9 years period.
The demographic data, complications, length of hospital ...admission related to PEG insertion and follow-up findings of 39 patients who had undergone percutaneous endoscopic gastrostomy using the standard pull-through technique between 2011 and 2020 were examined. The study took place at the Gastroenterology Division, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia RESULTS: The most common indications of feeding with a gastrostomy tube include neurological diseases (n=30, 76.9%), followed by metabolic disorders (n=3, 7.69%), chronic diarrhea (n=2, 5.1%), chronic kidney diseases (n=2, 5.1%), cystic fibrosis (n=1, 2.56%), feeding aversion fibrosis (n=1, 2.56%). Out of the 39 patients, 20 (51%) did not have any complications. However, minor complication are expected. Most common complications included local infection (n=14, 35.89%) followed by granulation tissue (n=6, 15.38%), "buried bumper syndrome" developed in one.
Percutaneous endoscopic gastrostomy tube is the desirable method for patients who are unable to feed orally, feeding is not adequate for demands, has special feeding requirements, or swallowing dysfunction. The technique has become more widespread because of its simplicity, safety, and low cost. Major complications are rare. The procedure is safe and effective and could be carried out by pediatric gastroenterologists after training.
Objectives: To evaluate the demographic data and complications in children who had undergone percutaneous endoscopic gastrostomy (PEG) over 9 years period. Methods: The demographic data, ...complications, length of hospital admission related to PEG insertion and follow-up findings of 39 patients who had undergone percutaneous endoscopic gastrostomy using the standard pull-through technique between 2011 and 2020 were examined. The study took place at the Gastroenterology Division, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Results: The most common indications of feeding with a gastrostomy tube include neurological diseases (n=30, 76.9%), followed by metabolic disorders (n=3, 7.69%), chronic diarrhea (n=2, 5.1%), chronic kidney diseases (n=2, 5.1%), cystic fibrosis (n=1, 2.56%), feeding aversion fibrosis (n=1, 2.56%). Out of the 39 patients, 20 (51%) did not have any complications. However, minor complication are expected. Most common complications included local infection (n=14, 35.89%) followed by granulation tissue (n=6, 15.38%), “buried bumper syndrome” developed in one. Conclusion: Percutaneous endoscopic gastrostomy tube is the desirable method for patients who are unable to feed orally, feeding is not adequate for demands, has special feeding requirements, or swallowing dysfunction. The technique has become more widespread because of its simplicity, safety, and low cost. Major complications are rare. The procedure is safe and effective and could be carried out by pediatric gastroenterologists after training.
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