Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked hypophosphatemia, currently one of the most prevalent varieties of familiar rickets, is attributed to renal phosphate wasting secondary to a gene defect localized to X p22 chromosomal region. The proximal tubular phosphate reabsorption defect is associated with blunted 1,25-dihydroxyvitamin D synthesis to hypophosphatemia or parathyroid hormone administration. It is characterized clinically by hypophosphatemia, growth retardation, and rickets especially in male patients. As the affected patients mature, pseudofractures, skeletal deformities, osteomalacic bone pain, progressive ankylosis, and dental caries occur, which may be alleviated and even prevented with adequate medical therapy. Long term treatment combines phosphate supplementation with calcitriol, augmented occasionally by diuretics. Hypercalcemia, hyperparathyroidism, and nephrocalcinosis are potential complications which require careful monitoring and continued investigations. The use of recombinant human growth hormone to augment renal tubular reabsorption of phosphate and to promote linear growth remains to be examined in well controlled, clinical trials.
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PMID:X-linked hypophosphatemia: molecular biology and treatment controversies. 804

X-linked dominant hypophosphatemic rickets (XLHR), is characterized mainly by renal phosphate wasting with hypophosphatemia, short stature and abnormal bone mineralization. PHEX, located at Xp22.1-p22.2, is the gene causing XLHR. We aim to characterize the pathogenesis of a Chinese boy who is apparently 'heterozygous' in PHEX gene. Direct sequencing showed two peaks: one was a wild-type 'G' and the other was one base substitution to 'A', though the patient was a male. TA clone assay clearly showed each sequences and the ratios. The mutation effect was predicted via bioinformatics and validated by exon-trapping assay. Real-time PCR was applied to determine the copy number of PHEX. TA clone assay showed the frequency of normal (G) to mutant allele (A) as 19:13. Normal karyotype and real-time PCR results indicate the normal copy number of PHEX. This splice site mutation leads to 4 bp of exon 18 skipping out causing frame shift p.Gly590Glufs*28 that ends up with a loss of active site and Zn(2+)-binding site of PHEX, which probably interfere with renal phosphate reabsorption and bone mineralization. In conclusion, mutation at conserved splice acceptor site resulted in aberrant splicing, ending up with a damaged protein product. This novel mutation is de novo in mosaic pattern that may be induced during early postzygotic period. Taking mosaic somatic mutation of PHEX into consideration is strongly suggested in genetic counseling and etiology research for XLHR.
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PMID:A de novo mosaic mutation of PHEX in a boy with hypophosphatemic rickets. 2655 51