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Novel and recurrent mutations of WISP3 in two Chinese families with progressive pseudorheumatoid dysplasia.

Sun J, Xia W, He S, Zhao Z, Nie M, Li M, Jiang Y, Xing X, Wang O, Meng X, Zhou X - PLoS ONE (2012)

Bottom Line: The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities.All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations.The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

ABSTRACT

Background: The WNT1-inducible signaling pathway protein 3 (WISP3), which belongs to the CCN (cysteine-rich protein 61, connective tissue growth factor, nephroblastoma overexpressed) family, is a secreted cysteine-rich matricellular protein that is involved in chondrogenesis, osteogenesis and tumorigenesis. WISP3 gene mutations are associated with progressive pseudorheumatoid dysplasia (PPD, OMIM208230), an autosomal recessive genetic disease that is characterized by the swelling of multiple joints and disproportionate dwarfism.

Methodology/principal findings: Four PPD patients from two unrelated Chinese families were recruited for this study. The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities. WISP3 mutations were detected by direct DNA sequence analysis. In total, four different mutations were identified, which consisted of two missense mutations, one deletion and one insertion that spanned exons 3, 5 and 6 of the WISP3 gene. One of the missense mutations (c.342T>G/p.C114W) and a seven-base pair frameshift deletion (c.716_722del/p.E239fs*16) were novel. The other missense mutation (c.1000T>C/p. S334P) and the insertion mutation (c.866_867insA/p.Q289fs*31) had previously been identified in Chinese patients. All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations.

Conclusions/significance: The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3.

Show MeSH

Related in: MedlinePlus

The photographs and X-ray images of the proband in family 1.(A&B) Short-trunk disproportionate dwarfism and enlargement of the elbow and genual joints; (C) platyspondyly and ovoid anterior end-plate of vertebral bodies; (D) widened tibial metaphysis; (E) widened cubital metaphysis; (F) a normal pelvis at 5 years of age.
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pone-0038643-g001: The photographs and X-ray images of the proband in family 1.(A&B) Short-trunk disproportionate dwarfism and enlargement of the elbow and genual joints; (C) platyspondyly and ovoid anterior end-plate of vertebral bodies; (D) widened tibial metaphysis; (E) widened cubital metaphysis; (F) a normal pelvis at 5 years of age.

Mentions: The proband (II 2 in family 1), a 5-year-old boy, was referred to our clinic in October 2005. His parents communicated the boy's complaint of multiple joint swelling, which began at the age of 4. The swelling first affected the proximal interphalangeal joints, and subsequently, the metacarpophalangeal and distal interphalangeal joints. During the initial examination, the boy presented with a minimal fusiform swelling of the metacarpophalangeal and interphalangeal joints and a slight limitation in the extension of his fingers, and his height was in the 10th–25th percentile for his age. He was re-evaluated by us at the age of 10 after developing bilateral swelling and stiffness in his elbow, knee and ankle joints. At this time, his height was below the 3rd percentile for his age (shown in Figures 1A and B). The boy did not complain of pain in his hands, legs or back. X-ray images (at 5 years old) revealed a platyspondyly and ovoid anterior end-plate of the vertebral bodies on the thoracolumbar spine, a widened elbow and tibial metaphysis. An enlargement of epiphysis did not exist, and the pelvis appeared normal (shown in Figures 1C–F).


Novel and recurrent mutations of WISP3 in two Chinese families with progressive pseudorheumatoid dysplasia.

Sun J, Xia W, He S, Zhao Z, Nie M, Li M, Jiang Y, Xing X, Wang O, Meng X, Zhou X - PLoS ONE (2012)

The photographs and X-ray images of the proband in family 1.(A&B) Short-trunk disproportionate dwarfism and enlargement of the elbow and genual joints; (C) platyspondyly and ovoid anterior end-plate of vertebral bodies; (D) widened tibial metaphysis; (E) widened cubital metaphysis; (F) a normal pelvis at 5 years of age.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369844&req=5

pone-0038643-g001: The photographs and X-ray images of the proband in family 1.(A&B) Short-trunk disproportionate dwarfism and enlargement of the elbow and genual joints; (C) platyspondyly and ovoid anterior end-plate of vertebral bodies; (D) widened tibial metaphysis; (E) widened cubital metaphysis; (F) a normal pelvis at 5 years of age.
Mentions: The proband (II 2 in family 1), a 5-year-old boy, was referred to our clinic in October 2005. His parents communicated the boy's complaint of multiple joint swelling, which began at the age of 4. The swelling first affected the proximal interphalangeal joints, and subsequently, the metacarpophalangeal and distal interphalangeal joints. During the initial examination, the boy presented with a minimal fusiform swelling of the metacarpophalangeal and interphalangeal joints and a slight limitation in the extension of his fingers, and his height was in the 10th–25th percentile for his age. He was re-evaluated by us at the age of 10 after developing bilateral swelling and stiffness in his elbow, knee and ankle joints. At this time, his height was below the 3rd percentile for his age (shown in Figures 1A and B). The boy did not complain of pain in his hands, legs or back. X-ray images (at 5 years old) revealed a platyspondyly and ovoid anterior end-plate of the vertebral bodies on the thoracolumbar spine, a widened elbow and tibial metaphysis. An enlargement of epiphysis did not exist, and the pelvis appeared normal (shown in Figures 1C–F).

Bottom Line: The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities.All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations.The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

ABSTRACT

Background: The WNT1-inducible signaling pathway protein 3 (WISP3), which belongs to the CCN (cysteine-rich protein 61, connective tissue growth factor, nephroblastoma overexpressed) family, is a secreted cysteine-rich matricellular protein that is involved in chondrogenesis, osteogenesis and tumorigenesis. WISP3 gene mutations are associated with progressive pseudorheumatoid dysplasia (PPD, OMIM208230), an autosomal recessive genetic disease that is characterized by the swelling of multiple joints and disproportionate dwarfism.

Methodology/principal findings: Four PPD patients from two unrelated Chinese families were recruited for this study. The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities. WISP3 mutations were detected by direct DNA sequence analysis. In total, four different mutations were identified, which consisted of two missense mutations, one deletion and one insertion that spanned exons 3, 5 and 6 of the WISP3 gene. One of the missense mutations (c.342T>G/p.C114W) and a seven-base pair frameshift deletion (c.716_722del/p.E239fs*16) were novel. The other missense mutation (c.1000T>C/p. S334P) and the insertion mutation (c.866_867insA/p.Q289fs*31) had previously been identified in Chinese patients. All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations.

Conclusions/significance: The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3.

Show MeSH
Related in: MedlinePlus