Abstract
Objective. Homozygous recessive germline mutations of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene, encoding 15-hydroxyprostaglandin dehydrogenase, result in persistent elevation of circulating PGE2 levels, causing the syndrome of primary hypertrophic osteoarthropathy (PHO). Homozygous HPGD mutations have so far been reported in 10 families, all but one displaying parental consanguinity. Only two of these families were of European origin. We wished to determine the role of HPGD in causing PHO in non-consanguineous European families. Methods. Five previously unreported families of Caucasian European origin, with one or more individuals affected with typical PHO, were characterized clinically and by complete sequencing of the HPGD coding exons. Results. Biallelic HPGD mutations were identified in affected individuals in all the five families, confirming a very specific association of this phenotype with HPGD mutations. The previously described c.175_176delCT frameshift mutation was observed in association with two different alleles of an adjacent single nucleotide polymorphism. Conclusions. Biallelic HPGD mutations are found in the majority of patients with typical PHO, and sequencing of the HPGD gene is a highly specific first-line investigation for patients presenting in this way, particularly during childhood. The c.175_176delCT frameshift mutation appears to be recurrent and to be the commonest HPGD mutation in Caucasian families.
| Original language | English (US) |
|---|---|
| Article number | keq048 |
| Pages (from-to) | 1056-1062 |
| Number of pages | 7 |
| Journal | Rheumatology |
| Volume | 49 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 18 2010 |
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Keywords
- 15-hydroxyprostaglandin dehydrogenase
- Clubbing
- Primary hypertrophic osteoarthropathy
- Prostaglandin
ASJC Scopus subject areas
- Rheumatology
- Pharmacology (medical)
Cite this
Common and recurrent HPGD mutations in Caucasian individuals with primary hypertrophic osteoarthropathy. / Diggle, Christine P.; Carr, Ian M.; Zitt, Emanuel; Wusik, Katie; Hopkin, Robert J.; Prada, Carlos E.; Calabrese, Olga; Rittinger, Olaf; Punaro, Marilynn G.; Markham, Alexander F.; Bonthron, David T.
In: Rheumatology, Vol. 49, No. 6, keq048, 18.03.2010, p. 1056-1062.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Common and recurrent HPGD mutations in Caucasian individuals with primary hypertrophic osteoarthropathy
AU - Diggle, Christine P.
AU - Carr, Ian M.
AU - Zitt, Emanuel
AU - Wusik, Katie
AU - Hopkin, Robert J.
AU - Prada, Carlos E.
AU - Calabrese, Olga
AU - Rittinger, Olaf
AU - Punaro, Marilynn G.
AU - Markham, Alexander F.
AU - Bonthron, David T.
PY - 2010/3/18
Y1 - 2010/3/18
N2 - Objective. Homozygous recessive germline mutations of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene, encoding 15-hydroxyprostaglandin dehydrogenase, result in persistent elevation of circulating PGE2 levels, causing the syndrome of primary hypertrophic osteoarthropathy (PHO). Homozygous HPGD mutations have so far been reported in 10 families, all but one displaying parental consanguinity. Only two of these families were of European origin. We wished to determine the role of HPGD in causing PHO in non-consanguineous European families. Methods. Five previously unreported families of Caucasian European origin, with one or more individuals affected with typical PHO, were characterized clinically and by complete sequencing of the HPGD coding exons. Results. Biallelic HPGD mutations were identified in affected individuals in all the five families, confirming a very specific association of this phenotype with HPGD mutations. The previously described c.175_176delCT frameshift mutation was observed in association with two different alleles of an adjacent single nucleotide polymorphism. Conclusions. Biallelic HPGD mutations are found in the majority of patients with typical PHO, and sequencing of the HPGD gene is a highly specific first-line investigation for patients presenting in this way, particularly during childhood. The c.175_176delCT frameshift mutation appears to be recurrent and to be the commonest HPGD mutation in Caucasian families.
AB - Objective. Homozygous recessive germline mutations of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene, encoding 15-hydroxyprostaglandin dehydrogenase, result in persistent elevation of circulating PGE2 levels, causing the syndrome of primary hypertrophic osteoarthropathy (PHO). Homozygous HPGD mutations have so far been reported in 10 families, all but one displaying parental consanguinity. Only two of these families were of European origin. We wished to determine the role of HPGD in causing PHO in non-consanguineous European families. Methods. Five previously unreported families of Caucasian European origin, with one or more individuals affected with typical PHO, were characterized clinically and by complete sequencing of the HPGD coding exons. Results. Biallelic HPGD mutations were identified in affected individuals in all the five families, confirming a very specific association of this phenotype with HPGD mutations. The previously described c.175_176delCT frameshift mutation was observed in association with two different alleles of an adjacent single nucleotide polymorphism. Conclusions. Biallelic HPGD mutations are found in the majority of patients with typical PHO, and sequencing of the HPGD gene is a highly specific first-line investigation for patients presenting in this way, particularly during childhood. The c.175_176delCT frameshift mutation appears to be recurrent and to be the commonest HPGD mutation in Caucasian families.
KW - 15-hydroxyprostaglandin dehydrogenase
KW - Clubbing
KW - Primary hypertrophic osteoarthropathy
KW - Prostaglandin
UR - http://www.scopus.com/inward/record.url?scp=77953551232&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953551232&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/keq048
DO - 10.1093/rheumatology/keq048
M3 - Article
C2 - 20299379
AN - SCOPUS:77953551232
VL - 49
SP - 1056
EP - 1062
JO - Rheumatology (United Kingdom)
JF - Rheumatology (United Kingdom)
SN - 1462-0324
IS - 6
M1 - keq048
ER -