Clinical phenotype and genetic analysis of a case of progressive pseudorheumatoid dysplasia caused by CCN6 compound heterozygous mutations and literature review
10.3760/cma.j.cn511374-20250331-00189
- VernacularTitle:CCN6基因复合杂合变异致进行性假性类风湿发育不良1例患者的临床表型与遗传学分析并文献复习
- Author:
Mengyu WANG
1
;
Qiaofeng MA
;
Zhenhong ZHANG
;
Li CHEN
;
Jidong LIU
Author Information
1. 山东大学齐鲁医院，内分泌与代谢病科，济南 250012
- Publication Type:Journal Article
- Keywords:
Progressive pseudorheumatoid dysplasia;
Epiphyseal dysplasia;
Cellular communication network factor 6;
Gene variation
- From:
Chinese Journal of Medical Genetics
2025;42(9):1141-1150
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical phenotype and genetic characteristics of a patient with Progressive pseudorheumatoid dysplasia (PPRD) due to compound heterozygous variants of CCN6 gene. Methods:A patient who was admitted to Qilu Hospital of Shandong University due to " bilateral finger joint deformity, bilateral hip and knee joint movement limitation for 19 years" was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and her parents and subjected to whole exome sequencing (WES). Long-read sequencing (LRS) and Sanger sequencing were used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Ethics No.: KYLL-202502 061).Results:The patient, a 23-year-old female, presented with progressive polyarticular deformity, limited movement and abnormal growth and development since childhood. She was initially misdiagnosed as Ankylosing spondylitis and had poor response to sulphasalazine and etoricoxib treatment. WES revealed that she has harbored two heterozygous variants of the CCN6 gene (NM_198239.2), namely c. 348C>A and c. 676G>C. LRS confirmed that the two variants are located on two homologous chromosomes and constitute compound heterozygous variants. Based on the ACMG guidelines, both variants were rated as pathogenic (PVS1+ PM2_Supporting+ PM3; PM1+ PM2_Supporting+ PM3_Supporting+ PM5+ PP3_Strong). The c. 676G>C variant has not been recorded by the HGMD and ClinVar databases. Conclusion:The c. 348C>A and c. 676G>C compound heterozygous variants of the CCN6 gene probably underlay the pathogenesis of PPRD in this patient. Above finding has enriched the mutational spectrum of PPRD and provided a basis for the clinical diagnosis and genetic counseling.
