Hu Qiongyi, Liu Jing, Wang Yi, Wang Jiucun, Shi Hui, Sun Yue, Wu Xinyao, Yang Chengde, Teng Jialin
Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
State Key Laboratory of Genetic Engineering and Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
BMC Med Genet. 2017 Dec 15;18(1):149. doi: 10.1186/s12881-017-0507-3.
Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive genetic disease that is characterized by pain, stiffness and enlargement of multiple joints with an age of onset between 3 and 8 years old. Mutations in the WISP3 (Wnt1-inducible signal pathway) gene are known to be the cause of PPD.
We present a case of delayed-onset PPD in a Chinese man. The 35-year-old proband presented with an almost 20-year history of pain and limitations in mobility in multiple joints. Based on the clinical manifestations, the patient was diagnosed with PPD; however, there was no specific evidence to confirm this diagnosis. Through mutational analyses, two WIPS3 mutations in exon 4, including a novel frameshift mutation (c.670dupA) in the paternal allele and an already described nonsense mutation (c.756C > A, p.Cys252*) in the maternal allele, were identified in the proband. Thus, the patient was diagnosed with PPD. Furthermore, we found that the proband's son only carried one of the mutations (c.670dupA) and therefore determined that he would not be affected by PPD in the future.
In this case, we successfully diagnosed the disease that the proband was affected precisely after the reunion of clinical diagnosis and genetic analysis. These findings demonstrate the clinical utility of genetic analysis to diagnose skeletal dysplasia and guide genetic counseling.
进行性假类风湿性发育不良（PPD）是一种罕见的常染色体隐性遗传病，其特征为多关节疼痛、僵硬和肿大，发病年龄在3至8岁之间。已知WISP3（Wnt1诱导信号通路）基因的突变是PPD的病因。
我们报告一例中国男性迟发性PPD病例。这位35岁的先证者有近20年的多关节疼痛和活动受限病史。根据临床表现，该患者被诊断为PPD；然而，没有具体证据证实这一诊断。通过突变分析，在先证者中发现外显子4中的两个WIPS3突变，包括父本等位基因中的一个新的移码突变（c.670dupA）和母本等位基因中一个已描述的无义突变（c.756C＞A，p.Cys252*）。因此，该患者被诊断为PPD。此外，我们发现先证者的儿子只携带其中一个突变（c.670dupA），因此确定他将来不会受到PPD的影响。
在本病例中，我们成功地在临床诊断与基因分析相结合后准确诊断出先证者所患疾病。这些发现证明了基因分析在诊断骨骼发育不良和指导遗传咨询方面的临床实用性。
