Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia multiple epiphyseal dysplasia disease spectrum
Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia multiple epiphyseal dysplasia disease spectrum
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DOI：
10.1086/301713
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发表时间：
1998-02-01
影响因子：
9.8
通讯作者：
Cohn, DH
中科院分区：
文献类型：
--
作者：
Briggs, MD;Mortier, GR;Cohn, DH
假性软骨发育不全（PSACH）和多发性骨骺发育不良（MED）是常染色体显性骨软骨发育不良，导致轻度至重度短肢侏儒症和早发性骨关节病。PSACH和某些形式的MED由软骨寡聚基质蛋白基因的突变引起（COMP; OMIM 600310 [http://www3.ncbi.nlm.nih.gov:80/ htbin-post/Omim/dispmim？600310]）。我们报告了在另外14个具有PRACH或MED表型的家族中鉴定COMP突变。预测导致单氨基酸缺失或取代的突变，都在编码钙调素样重复元件的COMP基因区域，在中度至重度PRACH患者中鉴定。我们还确定了在这个域的错义突变，产生MED费尔班克。在两个家庭中，一个与轻度PSACH和第二个与MED的形式，我们确定了不同的取代的残基在羧基末端球状区的COMP。这两个家庭的临床表现和COMP基因突变的鉴定提供证据PSACH和MED之间的表型重叠。这些数据也揭示了羧基末端结构域的结构和/或功能的COMP的作用。
Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are autosomal dominant osteochondrodysplasias that result in mild to severe short-limb dwarfism and early-onset osteoarthrosis. PSACH and some forms of MED result from mutations in the gene for cartilage oligomeric matrix protein (COMP; OMIM 600310 [http://www3.ncbi.nlm.nih.gov:80/ htbin-post/Omim/dispmim?600310]). We report the identification of COMP mutations in an additional 14 families with PSACH or MED phenotypes. Mutations predicted to result in single-amino acid deletions or substitutions, all in the region of the COMP gene encoding the calmodulin-like repeat elements, were identified in patients with moderate to severe PSACH. We also identified within this domain a missense mutation that produced MED Fairbank. In two families, one with mild PSACH and the second with a form of MED, we identified different substitutions for a residue in the carboxyl-terminal globular region of COMP. Both the clinical presentations of these two families and the identification of COMP-gene mutations provide evidence of phenotypic overlap between PSACH and MED. These data also reveal a role for the carboxyl-terminal domain in the structure and/or function of COMP.