Limits...
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 pedigrees and automated sequencing traces of the WISP3 gene mutations in the two families in our study.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3369844&req=5

pone-0038643-g005: The pedigrees and automated sequencing traces of the WISP3 gene mutations in the two families in our study.

Mentions: The same compound heterozygous WISP3 mutation occurred in patients II 1 and II 2 as follows (Figure 5): 1. a missense mutation c.1000T>C in exon 6, which was the transition of a single nucleotide T→C that caused the amino acid serine (TCT) in codon 334 to change to proline (CCT); this mutation was also detected in the heterozygous state in their father; and 2. a frameshift mutation c.866_867insA in exon 6, which was an insertion of a nucleotide in codon 289 (glutamine) of the WISP3 gene that caused a frame shift of the coding region; this mutation was also detected in the heterozygous state in their mother.


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 pedigrees and automated sequencing traces of the WISP3 gene mutations in the two families in our study.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038643-g005: The pedigrees and automated sequencing traces of the WISP3 gene mutations in the two families in our study.
Mentions: The same compound heterozygous WISP3 mutation occurred in patients II 1 and II 2 as follows (Figure 5): 1. a missense mutation c.1000T>C in exon 6, which was the transition of a single nucleotide T→C that caused the amino acid serine (TCT) in codon 334 to change to proline (CCT); this mutation was also detected in the heterozygous state in their father; and 2. a frameshift mutation c.866_867insA in exon 6, which was an insertion of a nucleotide in codon 289 (glutamine) of the WISP3 gene that caused a frame shift of the coding region; this mutation was also detected in the heterozygous state in their mother.

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