The first case of primary hypertrophic osteoarthropathy with soft tissue giant tumors caused by HPGD loss-of-function mutation.
COX2 selective inhibitor treatment
HPGD mutation
PHO
primary hypertrophic osteoarthropathy
soft tumor
Journal
Endocrine connections
ISSN: 2049-3614
Titre abrégé: Endocr Connect
Pays: England
ID NLM: 101598413
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
14
04
2019
accepted:
07
05
2019
pubmed:
8
5
2019
medline:
8
5
2019
entrez:
8
5
2019
Statut:
ppublish
Résumé
Primary hypertrophic osteoarthropathy (PHO) is a rare genetic multi-organic disease characterized by digital clubbing, periostosis and pachydermia. Two genes, HPGD and SLCO2A1, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and prostaglandin transporter (PGT), respectively, have been reported to be related to PHO. Deficiency of aforementioned two genes leads to failure of prostaglandin E2 (PGE2) degradation and thereby elevated levels of PGE2. PGE2 plays an important role in tumorigenesis. Studies revealed a tumor suppressor activity of 15-PGDH in tumors, such as lung, bladder and breast cancers. However, to date, no HPGD-mutated PHO patients presenting concomitant tumor has been documented. In the present study, we reported the first case of HPGD-mutated PHO patient with soft tissue giant tumors at lower legs and evaluated the efficacy of selective COX-2 inhibitor (etoricoxib) treatment in the patient. In this study, we summarized the clinical data, collected the serum and urine samples for biochemical test and analyzed the HPGD gene in our patient. A common HPGD mutation c.310_311delCT was identified in the patient. In addition to typical clinical features (digital clubbing, periostosis and pachydermia), the patient demonstrated a new clinical manifestation, a giant soft tissue tumor on the left lower leg which has not been reported in HPGD-mutated PHO patient before. After 6-month treatment with etoricoxib, the patient showed decreased PGE2 levels and improved PHO-related symptoms. Though the soft tissue tumor persisted, it seemed to be controlled under the etoricoxib treatment. This finding expanded the clinical spectrum of PHO and provided unique insights into the HPGD-mutated PHO.
Sections du résumé
BACKGROUND
BACKGROUND
Primary hypertrophic osteoarthropathy (PHO) is a rare genetic multi-organic disease characterized by digital clubbing, periostosis and pachydermia. Two genes, HPGD and SLCO2A1, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and prostaglandin transporter (PGT), respectively, have been reported to be related to PHO. Deficiency of aforementioned two genes leads to failure of prostaglandin E2 (PGE2) degradation and thereby elevated levels of PGE2. PGE2 plays an important role in tumorigenesis. Studies revealed a tumor suppressor activity of 15-PGDH in tumors, such as lung, bladder and breast cancers. However, to date, no HPGD-mutated PHO patients presenting concomitant tumor has been documented. In the present study, we reported the first case of HPGD-mutated PHO patient with soft tissue giant tumors at lower legs and evaluated the efficacy of selective COX-2 inhibitor (etoricoxib) treatment in the patient.
METHODS
METHODS
In this study, we summarized the clinical data, collected the serum and urine samples for biochemical test and analyzed the HPGD gene in our patient.
RESULTS
RESULTS
A common HPGD mutation c.310_311delCT was identified in the patient. In addition to typical clinical features (digital clubbing, periostosis and pachydermia), the patient demonstrated a new clinical manifestation, a giant soft tissue tumor on the left lower leg which has not been reported in HPGD-mutated PHO patient before. After 6-month treatment with etoricoxib, the patient showed decreased PGE2 levels and improved PHO-related symptoms. Though the soft tissue tumor persisted, it seemed to be controlled under the etoricoxib treatment.
CONCLUSION
CONCLUSIONS
This finding expanded the clinical spectrum of PHO and provided unique insights into the HPGD-mutated PHO.
Identifiants
pubmed: 31063976
doi: 10.1530/EC-19-0149
pii: EC-19-0149.R1
pmc: PMC6547301
doi:
pii:
Types de publication
Journal Article
Langues
eng
Pagination
736-744Références
Am J Hum Genet. 2012 Jan 13;90(1):125-32
pubmed: 22197487
Cancer Prev Res (Phila). 2008 Jul;1(2):77-9
pubmed: 19138938
Biochemistry. 1995 May 9;34(18):6003-13
pubmed: 7742302
Rheumatol Int. 2014 Nov;34(11):1539-44
pubmed: 24816859
Calcif Tissue Int. 2015 Oct;97(4):336-42
pubmed: 26135126
PLoS One. 2010 Nov 02;5(11):e13719
pubmed: 21072165
J Cancer Res Clin Oncol. 2013 May;139(5):797-807
pubmed: 23385883
J Dermatol Sci. 2015 May;78(2):151-3
pubmed: 25680852
Cancer Metastasis Rev. 2011 Dec;30(3-4):449-63
pubmed: 22002714
Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17468-73
pubmed: 15574495
Bone. 2018 Jan;106:96-102
pubmed: 28963081
Cancer Prev Res (Phila). 2014 Aug;7(8):805-12
pubmed: 24838973
Oncol Lett. 2014 Oct;8(4):1589-1594
pubmed: 25202373
Am J Pathol. 2010 Mar;176(3):1462-8
pubmed: 20093479
Rheumatol Int. 2009 Nov;30(1):39-43
pubmed: 19306095
J Orthop Translat. 2018 Oct 31;18:109-118
pubmed: 31508314
Nat Genet. 2008 Jun;40(6):789-93
pubmed: 18500342
Mod Rheumatol. 2015 Mar;25(2):315-21
pubmed: 24533558
Bioorg Med Chem Lett. 2011 Oct 15;21(20):6071-3
pubmed: 21903394
J Biol Chem. 2015 Dec 11;290(50):29781-93
pubmed: 26475855
Ann Hum Genet. 2018 May;82(3):171-176
pubmed: 29282707
Gut. 2006 Jan;55(1):115-22
pubmed: 16118353
J Rheumatol. 2015 Nov;42(11):2211-4
pubmed: 26523041
Arch Med Res. 2001 Mar-Apr;32(2):136-42
pubmed: 11343811
J Biol Chem. 2005 Feb 4;280(5):3217-23
pubmed: 15542609
Mol Pharmacol. 2004 Apr;65(4):973-8
pubmed: 15044627
Clin Rheumatol. 2007 Jan;26(1):8-11
pubmed: 16738844
Pediatr Radiol. 2016 May;46(5):727-30
pubmed: 26939972
Rheumatology (Oxford). 2010 Jun;49(6):1056-62
pubmed: 20299379
Hum Mutat. 2012 Apr;33(4):660-4
pubmed: 22331663
Clin Exp Rheumatol. 1992 May-Jun;10 Suppl 7:27-33
pubmed: 1623669
J Biol Chem. 2007 Apr 20;282(16):11613-7
pubmed: 17329241
Biomed Res Int. 2015;2015:595273
pubmed: 26000299
J Med Genet. 2009 Jan;46(1):14-20
pubmed: 18805827
Hum Mutat. 2012 Aug;33(8):1175-81
pubmed: 22553128
Biochemistry. 1990 Jan 23;29(3):738-43
pubmed: 2337593
J Bone Miner Res. 2017 Aug;32(8):1659-1666
pubmed: 28425581
J Dermatol Sci. 2012 Oct;68(1):36-44
pubmed: 22906430
Eur J Hum Genet. 2009 Dec;17(12):1570-6
pubmed: 19568269
Cancer Prev Res (Phila). 2008 Jul;1(2):93-9
pubmed: 19138942
Int J Cell Biol. 2012;2012:723419
pubmed: 22505934
J Clin Endocrinol Metab. 2013 May;98(5):E923-33
pubmed: 23509104