Liang Hanting, Hou Yanfang, Pang Qianqian, Jiang Yan, Wang Ou, Li Mei, Xing Xiaoping, Zhu Huijuan, Xia Weibo
Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
Calcif Tissue Int. 2022 Mar;110(3):313-323. doi: 10.1007/s00223-021-00920-6. Epub 2021 Oct 28.
Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia type 1 (MED1) are two rare skeletal disorders caused by cartilage oligomeric matrix protein (COMP) variants. This study aims to analyze the genotype and phenotype of patients with COMP variants. Clinical information for 14 probands was collected; DNA was extracted from blood for COMP variant detection. Clinical manifestations and radiology scoring systems were established to evaluate the severity of each patient's condition. Serum COMP levels in PSACH patients and healthy subjects were measured. Thirty-nine patients were included, along with 12 PSACH probands and two MED1 probands. Disproportionate short stature, waddling gait, early-onset osteoarthritis and skeletal deformities were the most common features. The height Z-score of PSACH patients correlated negatively with age at evaluation (r = - 0.603, p = 0.01) and the clinical manifestation score (r = - 0.556, p = 0.039). Over 50% of the PSACH patients were overweight/obese. The median serum COMP level in PSACH patients was 16.75 ng/ml, which was significantly lower than that in healthy controls (98.53 ng/ml; p < 0.001). The condition of MED1 patients was better than that of PSACH patients. Four novel variants of COMP were detected: c.874T>C, c.1123_1134del, c.1531G>A, and c.1576G>T. Height Z-scores and serum COMP levels were significantly lower in patients carrying mutations located in calmodulin-like domains 6, 7, and 8. As the two phenotypes overlap to different degrees, PSACH and MED1 are suggested to combine to produce "spondyloepiphyseal dysplasia, COMP type". Clinical manifestations and radiology scoring systems, serum COMP levels and genotype are important for evaluating patient condition severity.
假性软骨发育不全（PSACH）和1型多发性骨骺发育不良（MED1）是由软骨寡聚基质蛋白（COMP）变异引起的两种罕见骨骼疾病。本研究旨在分析COMP变异患者的基因型和表型。收集了14名先证者的临床信息；从血液中提取DNA用于COMP变异检测。建立临床表现和放射学评分系统以评估每位患者的病情严重程度。测量了PSACH患者和健康受试者的血清COMP水平。共纳入39名患者，其中包括12名PSACH先证者和2名MED1先证者。身材不成比例矮小、蹒跚步态、早发性骨关节炎和骨骼畸形是最常见的特征。PSACH患者身高Z评分与评估时的年龄呈负相关（r = -0.603，p = 0.01），与临床表现评分呈负相关（r = -0.556，p = 0.039）。超过50%的PSACH患者超重/肥胖。PSACH患者血清COMP水平中位数为16.75 ng/ml，显著低于健康对照组（98.53 ng/ml；p < 0.001）。MED1患者的病情比PSACH患者好。检测到COMP的4种新变异：c.874T>C、c.1123_1134del、c.1531G>A和c.1576G>T。位于钙调蛋白样结构域6、7和8的突变携带者患者的身高Z评分和血清COMP水平显著较低。由于这两种表型存在不同程度的重叠，建议将PSACH和MED1合并为“COMP型脊椎骨骺发育不良”。临床表现和放射学评分系统、血清COMP水平和基因型对于评估患者病情严重程度很重要。
