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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 2.(A) Flattened vertebrae on the cervical spine and normal skull; (B) flattened vertebrae on the thoracic and lumbar spine with anterior beaking and an increased anteroposterior diameter of the vertebral bodies; (C) enlargement of the interphalangeal, metacarpal and metacarpophalangeal epiphyses; (D) narrow joint spaces and irregular articular surfaces of hip joints with short femoral necks; (E) slight enlargement of elbow epiphyses and metaphyses; (F) flattened talus with narrow joint spaces.
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pone-0038643-g003: The X-ray images of patient II 1 in family 2.(A) Flattened vertebrae on the cervical spine and normal skull; (B) flattened vertebrae on the thoracic and lumbar spine with anterior beaking and an increased anteroposterior diameter of the vertebral bodies; (C) enlargement of the interphalangeal, metacarpal and metacarpophalangeal epiphyses; (D) narrow joint spaces and irregular articular surfaces of hip joints with short femoral necks; (E) slight enlargement of elbow epiphyses and metaphyses; (F) flattened talus with narrow joint spaces.

Mentions: The proband (II 1 in family 2) was thought to be normal for his first few years of life. At the age of 5, swelling and then stiffness of the interphalangeal and metacarpophalangeal joints emerged. The knees, elbows and hips were all affected at the age of 12. At 14 years of age, the boy presented at the clinic with short-trunk disproportionate dwarfism, scoliosis and a waddling gait. X-ray images showed flattening vertebrae on the cervical, thoracic and lumbar spine with anterior beaking, an increased anteroposterior diameter of the vertebral bodies, enlargement of the interphalangeal, metacarpal, elbow, genual, ankle and femoral epiphyses with narrow joint spaces and irregular articular surfaces. The skull was normal (Figures 3A–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 X-ray images of patient II 1 in family 2.(A) Flattened vertebrae on the cervical spine and normal skull; (B) flattened vertebrae on the thoracic and lumbar spine with anterior beaking and an increased anteroposterior diameter of the vertebral bodies; (C) enlargement of the interphalangeal, metacarpal and metacarpophalangeal epiphyses; (D) narrow joint spaces and irregular articular surfaces of hip joints with short femoral necks; (E) slight enlargement of elbow epiphyses and metaphyses; (F) flattened talus with narrow joint spaces.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038643-g003: The X-ray images of patient II 1 in family 2.(A) Flattened vertebrae on the cervical spine and normal skull; (B) flattened vertebrae on the thoracic and lumbar spine with anterior beaking and an increased anteroposterior diameter of the vertebral bodies; (C) enlargement of the interphalangeal, metacarpal and metacarpophalangeal epiphyses; (D) narrow joint spaces and irregular articular surfaces of hip joints with short femoral necks; (E) slight enlargement of elbow epiphyses and metaphyses; (F) flattened talus with narrow joint spaces.
Mentions: The proband (II 1 in family 2) was thought to be normal for his first few years of life. At the age of 5, swelling and then stiffness of the interphalangeal and metacarpophalangeal joints emerged. The knees, elbows and hips were all affected at the age of 12. At 14 years of age, the boy presented at the clinic with short-trunk disproportionate dwarfism, scoliosis and a waddling gait. X-ray images showed flattening vertebrae on the cervical, thoracic and lumbar spine with anterior beaking, an increased anteroposterior diameter of the vertebral bodies, enlargement of the interphalangeal, metacarpal, elbow, genual, ankle and femoral epiphyses with narrow joint spaces and irregular articular surfaces. The skull was normal (Figures 3A–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