TITLE

Thirteen Chinese patients with sporadic Paget's disease of bone: clinical features, SQSTM1 mutation identification, and functional analysis

AUTHOR(S)
Gu, Jie-mei; Zhang, Zhen-Lin; Zhang, Hao; Hu, Wei-wei; Wang, Chun; Yue, Hua; Ke, Yao-hua; He, Jin-wei; Hu, Yun-qiu; Li, Miao; Liu, Yu-juan; Fu, Wen-zhen
PUB. DATE
September 2012
SOURCE
Journal of Bone & Mineral Metabolism;Sep2012, Vol. 30 Issue 5, p525
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
To increase awareness of the rarity of Paget's disease of bone (PDB) in the Chinese population, we characterized the clinical manifestations and features of 13 Chinese sporadic PDB patients. The clinical features of our Chinese PDB patients show similarities with cases reported in Western countries. The most common lesion sites were the pelvis, femur, and tibia; the next most common lesion sites were the spine and skull. Most patients had a higher serum alkaline phosphatase (ALP) level. Treatment with bisphosphonates was effective. In addition, we screened for PDB-causing mutations and performed a functional analysis in an attempt to elucidate the molecular pathogenesis of PDB. A total of 216 persons, including 13 sporadic PDB patients, three unaffected relatives of 1 patient, and 200 healthy donors, were recruited. All eight exons and exon-intron boundaries of the SQSTM1 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. We identified a 53-year-old man who harbored a heterozygous T-to-C transversion at position 1250 in exon 8 (1250T > C), which resulted in a methionine-to-threonine (ATG > ACG) substitution at codon 404 (M404T). The M404T mutant SQSTM1 protein exhibited increased NF-κB activation and drove a significantly increased number of osteoclast-like cells (OLCs) that formed in response to RANKL and an increased number of OLC nuclei. This is the first report of an SQSTM1 genetic mutation that contributes to the pathogenesis of PDB in Chinese patients. These results may partially explain the mechanism by which this SQSTM1 mutation contributes to the pathogenesis of sporadic PDB in Chinese patients.
ACCESSION #
79824431

 

Related Articles

  • Serum homocysteine, folate and vitamin B12 in patients with Paget’s disease of bone: the effect of zoledronic acid. Polyzos, Stergios A.; Anastasilakis, Athanasios D.; Efstathiadou, Zoe; Litsas, Ioannis; Kita, Marina; Panagiotou, Athanasios; Papatheodorou, Athanasios; Arsos, Georgios; Moralidis, Efstratios; Barmpalios, Georgios; Zafeiriadou, Efthimia; Triantafillidou, Efthimia; Makrigiannaki, Eleni; Terpos, Evangelos // Journal of Bone & Mineral Metabolism;May2010, Vol. 28 Issue 3, p314 

    High serum homocysteine (HCY) and indirectly deficiency of folate and/or vitamin B12 stimulate bone resorption and adversely affect collagen cross-linking. The aim of this study was the evaluation of serum levels of HCY, folate and vitamin B12 in patients with Paget’s disease of bone...

  • Diagnosis and Treatment of Paget's Disease of Bone. Schneider, Doron; Hoffman, Mary T.; Peterson, Jeanette A. // American Family Physician;5/15/2002, Vol. 65 Issue 10, p2069 

    Paget's disease of bone (also known as osteitis deformans) is a nonmalignant disease involving accelerated bone resorption followed by deposition of dense, chaotic, and ineffectively mineralized bone matrix. The origin of the disease is unknown, and it is frequently asymptomatic; however, the...

  • Sequestosome 1 (SQSTM1) mutations in Paget's disease of bone from the United States. Rhodes, Emily C.; Johnson-Pais, Teresa L.; Singer, Frederick R.; Ankerst, Donna P.; Bruder, Jan M.; Wisdom, Julie; Hoon, Dave S. B.; Lin, Emerald; Bone, Henry G.; Simcic, Kenneth J.; Leach, Robin J. // Calcified Tissue International;Apr2008, Vol. 82 Issue 4, p271 

    Paget's disease of bone (PDB) is a localized bone disease characterized by excessive bone resorption due to overactive osteoclasts. Seven genetic loci (PDB1-PDB7) have been reported for late-onset PDB. PDB3 is the only locus where a gene, sequestosome 1 (SQSTM1), has been identified. Mutations...

  • New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis. Crockett, J. C.; Mellis, D. J.; Scott, D. I.; Helfrich, M. H. // Osteoporosis International;Jan2011, Vol. 22 Issue 1, p1 

    Functional, biochemical and genetic studies have over the past decade identified many causative genes in the osteoclast diseases osteopetrosis and Paget's disease of bone. Here, we outline all osteoclast diseases and their genetic associations and then focus specifically on those diseases caused...

  • Bisphosphonates inhibit bone resorption. Dale, David C.; Federman, Daniel D. // Cortlandt Forum;07/25/97, Vol. 10 Issue 7, p19 

    States that bisphosphonates, synthetic analogues of pyrophosphate slow bone resorption by inhibiting the action of osteoclasts in Paget's disease. Alendronate therapy for women; Pamidronate therapy.

  • Detection of SQSTM1/P392L post-zygotic mutations in Paget's disease of bone. Guay-Bélanger, Sabrina; Picard, Sylvain; Gagnon, Edith; Morissette, Jean; Siris, Ethel; Orcel, Philippe; Brown, Jacques; Michou, Laëtitia // Human Genetics;Jan2015, Vol. 134 Issue 1, p53 

    Paget's disease of bone (PDB) is transmitted, in one-third of cases, in an autosomal dominant mode of inheritance with incomplete penetrance. The SQSTM1/P392L germinal mutation is the most common mutation associated with PDB. Given the focal nature of PDB, one team of investigators showed that...

  • SKULL MONOSTOTIC PAGET'S DISEASE OF BONE -CASE REPORT AND REVIEW OF THE LITERATURE. Poiana, Catalina; Carsote, Mara; Hortopan, D.; Coculescu, M. // Acta Endocrinologica (1841-0987);Jul-Sep2007, Vol. 3 Issue 3, p333 

    Paget's disease of bone is a metabolic skeleton disorder with different epidemiological patterns: increased incidence up to 3% of the Northern Caucasian population over the age of 55 or a very rare occurrence as in Asia. We present a case of a 69 years old female patient with diffuse bone pain,...

  • Early onset Paget's disease of bone caused by a novel mutation (78dup27) of the TNFRSF11A gene in a Chinese family. Yao-hua KE; Hua YUE; Jin-wei HE; Yu-juan LIU; Zhen-lin ZHANG // Acta Pharmacologica Sinica;Aug2009, Vol. 30 Issue 8, p1204 

    AbstractAim:A previous study showed that individuals of Japanese descent affected by early onset familial Paget's disease of bone (PDB) carried a 27-bp duplication at position 75 (75dup27) in the TNFRSF11A gene encoding RANK. Here we report the identification of a novel mutation (78dup27) in...

  • Genetic diseases.  // Nephrology Dialysis Transplantation;May2012 Supplement 2, Vol. 27 Issue suppl_2, pii320 

    No abstract available.

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics