Deere M, Sanford T, Francomano C A, Daniels K, Hecht J T
Department of Pediatrics, University of Texas Medical School at Houston, Houston, Texas 77225-0708, USA.
Am J Med Genet. 1999 Aug 27;85(5):486-90. doi: 10.1002/(sici)1096-8628(19990827)85:5<486::aid-ajmg10>3.0.co;2-o.
Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) are allelic disorders caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). PSACH is a dominant condition characterized by disproportionate short stature, joint laxity, and early-onset osteoarthritis. EDM1 is a less severe skeletal dysplasia associated with average to mild short stature, joint pain, and early-onset osteoarthritis. COMP is an extracellular matrix protein present in cartilage, ligament, and tendon tissues. Here, we report on nine novel mutations in COMP causing PSACH and EDM1. Four of these mutations are in exons 13C and 14 where no previous mutations had been reported. One of those mutations was identified in two separate EDM1 families. In addition, we have identified the first case of PSACH resulting from an expansion of the five aspartates in exon 17B. We are also reporting a mutation in a third PSACH family with somatic/germline mosaicism. Therefore, this report increases the range of mutations that cause PSACH and EDM1 and provides additional regions to target for mutational analysis.
假性软骨发育不全（PSACH）和多发性骨骺发育不良（EDM1）是由编码软骨寡聚基质蛋白（COMP）的基因突变引起的等位基因疾病。PSACH是一种显性疾病，其特征为身材比例失调、关节松弛和早发性骨关节炎。EDM1是一种不太严重的骨骼发育不良，与中度至轻度身材矮小、关节疼痛和早发性骨关节炎有关。COMP是一种存在于软骨、韧带和肌腱组织中的细胞外基质蛋白。在此，我们报告了导致PSACH和EDM1的COMP基因的九个新突变。其中四个突变位于外显子13C和14，此前未报道过这些位置有突变。其中一个突变在两个独立的EDM1家族中被发现。此外，我们还鉴定出首例由外显子17B中五个天冬氨酸扩增导致的PSACH病例。我们还报告了一个患有体细胞/生殖细胞镶嵌现象的第三个PSACH家族中的一个突变。因此，本报告增加了导致PSACH和EDM1的突变范围，并为突变分析提供了更多的靶向区域。
