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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.

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Related in: MedlinePlus

The X-ray images of patient II 1 in family 1.(G) Platyspondyly of the lumbar spine: the vertebral bodies are wedged anteriorly, and there are narrow disc spaces, irregular vertebral end-plates and short pedicles; (H) enlargement of the epiphyseal and metaphyseal portions of the metacarpals and phalanges; (I) bilateral femoral neck fractures and enlargement of the capital femoral epiphyses; (J) an enlargement of genual epiphyses.
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pone-0038643-g002: The X-ray images of patient II 1 in family 1.(G) Platyspondyly of the lumbar spine: the vertebral bodies are wedged anteriorly, and there are narrow disc spaces, irregular vertebral end-plates and short pedicles; (H) enlargement of the epiphyseal and metaphyseal portions of the metacarpals and phalanges; (I) bilateral femoral neck fractures and enlargement of the capital femoral epiphyses; (J) an enlargement of genual epiphyses.

Mentions: The patient II 1 in family 1 came to our clinic at the age of 20, with the same age of disease onset but more severe symptoms compared with the proband in family 1. He presented with joint deformities, a walking disability and secondary myatrophy at the age of 15. His radiographic images (at 15 years old) demonstrated flattening and anterior beaking of the thoracolumbar spine with an increased anteroposterior diameter of the vertebral bodies, irregular upper and lower end-plates, narrow disc spaces and short pedicles. Enlargements of the interphalangeal and genual epiphyses and a deformed pelvis with bilateral femoral neck fractures and enlarged capital femoral epiphyses were observed (shown in Figures 2G–J).


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 X-ray images of patient II 1 in family 1.(G) Platyspondyly of the lumbar spine: the vertebral bodies are wedged anteriorly, and there are narrow disc spaces, irregular vertebral end-plates and short pedicles; (H) enlargement of the epiphyseal and metaphyseal portions of the metacarpals and phalanges; (I) bilateral femoral neck fractures and enlargement of the capital femoral epiphyses; (J) an enlargement of genual epiphyses.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038643-g002: The X-ray images of patient II 1 in family 1.(G) Platyspondyly of the lumbar spine: the vertebral bodies are wedged anteriorly, and there are narrow disc spaces, irregular vertebral end-plates and short pedicles; (H) enlargement of the epiphyseal and metaphyseal portions of the metacarpals and phalanges; (I) bilateral femoral neck fractures and enlargement of the capital femoral epiphyses; (J) an enlargement of genual epiphyses.
Mentions: The patient II 1 in family 1 came to our clinic at the age of 20, with the same age of disease onset but more severe symptoms compared with the proband in family 1. He presented with joint deformities, a walking disability and secondary myatrophy at the age of 15. His radiographic images (at 15 years old) demonstrated flattening and anterior beaking of the thoracolumbar spine with an increased anteroposterior diameter of the vertebral bodies, irregular upper and lower end-plates, narrow disc spaces and short pedicles. Enlargements of the interphalangeal and genual epiphyses and a deformed pelvis with bilateral femoral neck fractures and enlarged capital femoral epiphyses were observed (shown in Figures 2G–J).

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