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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 patient II 2 in family 2.(G) The hands display interphalangeal joint swelling; (H) a swollen knee; (I) slight enlargement of the metacarpophalangeal epiphyses; (J) slight enlargement of the femoral and tibial epiphyses; (K) an increased anteroposterior diameter of the vertebral bodies and irregular vertebral end-plates.
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pone-0038643-g004: The photographs and X-ray images of patient II 2 in family 2.(G) The hands display interphalangeal joint swelling; (H) a swollen knee; (I) slight enlargement of the metacarpophalangeal epiphyses; (J) slight enlargement of the femoral and tibial epiphyses; (K) an increased anteroposterior diameter of the vertebral bodies and irregular vertebral end-plates.

Mentions: The patient II 2 in family 2 was examined at the age of 4 as part of the family study for his 14-year-old brother (The proband in family 2). Swelling of the interphalangeal articulations was found to be his first clinical abnormality. At his second clinic visit at the age of 6, subtle symptoms consisting of swelling of interphalangeal, metacarpophalangeal and knee joints without stiffness observed (Figures 4G and H). The radiological findings were an increased anteroposterior diameter of the vertebral bodies, irregular vertebral end-plates and a slight enlargement of the metaphyses in the distal femurs, proximal tibiae, phalanges and metacarpals (Figures 4I–K). The routine blood test results (i.e., erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, serum calcium levels, serum phosphorus levels, alkaline phosphatase, parathyroid hormone, vitamin D status and insulin-like growth factor 1) of these four patients were within the normal range.


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 patient II 2 in family 2.(G) The hands display interphalangeal joint swelling; (H) a swollen knee; (I) slight enlargement of the metacarpophalangeal epiphyses; (J) slight enlargement of the femoral and tibial epiphyses; (K) an increased anteroposterior diameter of the vertebral bodies and irregular vertebral end-plates.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038643-g004: The photographs and X-ray images of patient II 2 in family 2.(G) The hands display interphalangeal joint swelling; (H) a swollen knee; (I) slight enlargement of the metacarpophalangeal epiphyses; (J) slight enlargement of the femoral and tibial epiphyses; (K) an increased anteroposterior diameter of the vertebral bodies and irregular vertebral end-plates.
Mentions: The patient II 2 in family 2 was examined at the age of 4 as part of the family study for his 14-year-old brother (The proband in family 2). Swelling of the interphalangeal articulations was found to be his first clinical abnormality. At his second clinic visit at the age of 6, subtle symptoms consisting of swelling of interphalangeal, metacarpophalangeal and knee joints without stiffness observed (Figures 4G and H). The radiological findings were an increased anteroposterior diameter of the vertebral bodies, irregular vertebral end-plates and a slight enlargement of the metaphyses in the distal femurs, proximal tibiae, phalanges and metacarpals (Figures 4I–K). The routine blood test results (i.e., erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, serum calcium levels, serum phosphorus levels, alkaline phosphatase, parathyroid hormone, vitamin D status and insulin-like growth factor 1) of these four patients were within the normal range.

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