Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We extend the spectrum of phenotypes caused by mutations in the Wnt/Norrin coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) by identifying two novel types of mutation in related individuals whose presenting features were profound muscle hypotonia, mild mental retardation, blindness, and growth retardation. One mutation removes 6 out of 9 consecutive leucine residues in the LRP5 signal peptide (c.43_60del or p.Leu15_Leu20del), which impairs polypeptide entry into the endoplasmic reticulum (ER), trafficking to the cell membrane, and signal transduction. The second mutation resulted from nonhomologous recombination between Alu repeat sequences, which deleted exons 14-16 and would produce a nonfunctional, truncated, and frameshifted polypeptide, if expressed [chr11:g.(13871447_1387511)_(13879636_13879700)del (NW_925106.1) or p.Pro1010GlnfsX38]. We confirmed that the length of the LRP5 signal peptide poly-leucine repeat is polymorphic in the general population, and, importantly, we were able to demonstrate in independent in vitro assays that different allele sizes affect receptor processing and signal transduction. Consequently, this polymorphism may have physiologic effects in vivo. This latter finding is relevant since through a genomewide search we identified nearly 400 human proteins that contain poly-leucine repeats within their signal peptide. We chose 18 of these proteins and genotyped the underlying trinucleotide repeat in healthy Caucasian individuals. More than one length allele was observed in one-half of the proteins. We therefore propose that natural variation in poly-leucine-stretches within signal peptides constitutes a currently unrecognized source of variability in protein translation and expression.
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PMID:A mutation in the signal sequence of LRP5 in a family with an osteoporosis-pseudoglioma syndrome (OPPG)-like phenotype indicates a novel disease mechanism for trinucleotide repeats. 1917 49

Patients with upper airway obstruction during sleep are at constant risk of hypoxic and hypercarbic episodes and are especially vulnerable during anaesthesia and sedation as the abnormal anatomy is compounded by drug-related respiratory depression. Elective procedures in patients with the obstructive sleep apnoea (OSA) should be usually delayed, allowing for the preoperative home treatment (diet, alcohol abstinence, nasal CPAP/BiPAP during night). Respiratory supportive techniques, started at home, should be continued in the hospital, both in preoperative and postoperative periods. Patients with OSA should be also thoroughly examined for possible anatomic abnormalities of the upper airway that may complicate laryngoscopy and/or intubation. Heavy premedication should be avoided; in special cases of very nervous patients oral clonidine may be used. Careful preoxygenation is mandatory, opioids should be used sparingly. Muscle relaxant should be calculated for an ideal body weight. Isoflurane should be avoided. The OPS and obese patients are usually extubated in the sitting or lateral positions to avoid limitation of FRC by elevated diaphragm. In selected cases, prolonged intubation and/or ventilation are recommended. Regional anaesthesia are usually safe in these patients, however, opioids should be used carefully. When sedation is required, ketamine or dexmedetomidine may be used.
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PMID:[Perioperative risk in patients with sleep apnoea]. 1946 21