Source:http://linkedlifedata.com/resource/pubmed/id/21426412
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2011-5-18
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| pubmed:abstractText |
Digital clubbing is the most prominent feature in primary (PHO) and secondary (pulmonary) hypertrophic osteoarthropathy (HO). Homozygous and compound heterozygous germline mutations in the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene encoding the major prostaglandin PGE2 catabolizing enzyme have been recently described in familial PHO cases. Elevated prostaglandin levels in affected individuals with cytokine-mediated tissue remodelling and vascular stimulation may underlie PHO and associated features as hyperhidrosis, acroosteolysis, pachyderma, periostosis and arthritis. We present clinical and biochemical data of three unrelated PHO families with HPGD mutations. The truncating mutation c.175_176del was found in two of our families and in one of the recently described pedigrees, all of European origin. We present evidence that c.175_176del is a recurrent mutation rather than an ancient founder allele. Two novel heterozygous HPGD mutations, the nonsense mutation c.118G>T (p.Glu40X) and the missense mutation c.563C>T (p.Thr188Ile), could be identified in a third family. We postulate that all HPGD mutations constitute loss-of-function alleles due to protein truncation or missense changes that affect hydrogen bonds lining the 15-PGDH enzyme reaction cavity. Elevated prostaglandin levels may give rise to use of non-steroidal anti-inflammatory drugs; however, therapeutic strategies have not been reported to date. Naproxen treatment in one of our mutation-positive patients resulted in alleviation of pain caused by periostosis and arthritis as well as reduction in substantially elevated prostaglandin levels, while no significant effects on digital clubbing, hyperhidrosis and pachyderma were observed. Further experience with nonsteroidal anti-inflammatory drugs in PHO is awaited.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
|
| pubmed:issn |
1600-0625
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| pubmed:author |
pubmed-author:BergmannCarstenC,
pubmed-author:FalkenbachAlbrechtA,
pubmed-author:GirschickHerman JHJ,
pubmed-author:HammHenningH,
pubmed-author:LassayLisaL,
pubmed-author:MorbachHennerH,
pubmed-author:OttHagenH,
pubmed-author:WittenhagenDietrichD,
pubmed-author:WobserMarionM,
pubmed-author:ZerresKlausK
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| pubmed:copyrightInfo |
© 2011 John Wiley & Sons A/S.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
20
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
531-3
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| pubmed:meshHeading |
pubmed-meshheading:21426412-Adolescent,
pubmed-meshheading:21426412-Aged,
pubmed-meshheading:21426412-Amino Acid Sequence,
pubmed-meshheading:21426412-Base Sequence,
pubmed-meshheading:21426412-Codon, Nonsense,
pubmed-meshheading:21426412-DNA Mutational Analysis,
pubmed-meshheading:21426412-Female,
pubmed-meshheading:21426412-Humans,
pubmed-meshheading:21426412-Hydroxyprostaglandin Dehydrogenases,
pubmed-meshheading:21426412-Hyperhidrosis,
pubmed-meshheading:21426412-Male,
pubmed-meshheading:21426412-Molecular Sequence Data,
pubmed-meshheading:21426412-Mutation,
pubmed-meshheading:21426412-Mutation, Missense,
pubmed-meshheading:21426412-Osteoarthropathy, Primary Hypertrophic,
pubmed-meshheading:21426412-Osteoarthropathy, Secondary Hypertrophic,
pubmed-meshheading:21426412-Pedigree,
pubmed-meshheading:21426412-Sequence Deletion,
pubmed-meshheading:21426412-Sequence Homology, Amino Acid
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| pubmed:year |
2011
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| pubmed:articleTitle |
Primary hypertrophic osteoarthropathy with digital clubbing and palmoplantar hyperhidrosis caused by 15-PGHD/HPGD loss-of-function mutations.
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| pubmed:publicationType |
Letter,
Case Reports
|