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


RESULTS
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
The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3.
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Jing
J
Sun
Weibo
W
Xia
Shuli
S
He
Zhen
Z
Zhao
Min
M
Nie
Mei
M
Li
Yan
Y
Jiang
Xiaoping
X
Xing
Ou
O
Wang
Xunwu
X
Meng
Xueying
X
Zhou
D001177:Arthropathy, Neurogenic / Q000000981:diagnostic imaging / Q000235:genetics*; D001483:Base Sequence; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics*; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007592:Joint Diseases / Q000151:congenital; D008297:Male; D016254:Mutagenesis, Insertional; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D011859:Radiography; D017384:Sequence Deletion; D055815:Young Adult
D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human