Genotype to phenotype correlations in cartilage oligomeric matrix protein associated chondrodysplasias.
Genotype to phenotype correlations in cartilage oligomeric matrix protein associated chondrodysplasias.
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DOI：
10.1038/ejhg.2014.30
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发表时间：
2014-11
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--
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中科院分区：
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假性软骨发育不全（PRACH）和常染色体显性遗传多发性骨骺发育不良（MED）是导致短肢侏儒症、关节疼痛和僵硬以及早发性骨关节炎的软骨发育不良。所有PRACH和MED的最大比例，导致软骨寡聚基质蛋白（COMP）的突变。1995年在PSACH和MED患者中首次发现COMP突变，随后有超过30篇出版物描述了至少250例PSACH-MED患者中的COMP突变。然而，尽管有这些发现，COMP突变和表型之间的关系还没有进行系统的分析。特别是，有，到目前为止，COMP突变的类型和位置之间的相关性很小，产生的表型PSACH或MED。为了确定基因型与表型的相关性，可以得出COMP，我们整理了300 COMP突变，包括25个最近发现的新突变。本分析的结果表明，在特定的残基和/或COMP的III型重复序列的区域的突变显着相关的PSACH或MED。这种新衍生的基因型表型相关性可能有助于确定PSACH和MED的预后，包括预测疾病的严重程度，并在长期指导遗传咨询，并有助于这些疾病的患者的临床管理。
Pseudoachondroplasia (PSACH) and autosomal dominant multiple epiphyseal dysplasia (MED) are chondrodysplasias resulting in short-limbed dwarfism, joint pain and stiffness and early onset osteoarthritis. All PSACH, and the largest proportion of MED, result from mutations in cartilage oligomeric matrix protein (COMP). The first mutations in COMP were identified in 1995 in patients with both PSACH and MED and subsequently there has been over 30 publications describing COMP mutations in at least 250 PSACH–MED patients. However, despite these discoveries, a methodical analysis of the relationship between COMP mutations and phenotypes has not been undertaken. In particular, there has, to date, been little correlation between the type and location of a COMP mutation and the resulting phenotype of PSACH or MED. To determine if genotype to phenotype correlations could be derived for COMP, we collated 300 COMP mutations, including 25 recently identified novel mutations. The results of this analysis demonstrate that mutations in specific residues and/or regions of the type III repeats of COMP are significantly associated with either PSACH or MED. This newly derived genotype to phenotype correlation may aid in determining the prognosis of PSACH and MED, including the prediction of disease severity, and in the long term guide genetic counselling and contribute to the clinical management of patients with these diseases.
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影响因子：
--
作者：
Piróg KA;Briggs MD
通讯作者：
Briggs MD
影响因子：
5.3
作者：
Ikegawa, S;Ohashi, H;Nakamura, Y
通讯作者：
Nakamura, Y
影响因子：
9.8
作者：
Briggs, MD;Mortier, GR;Cohn, DH
通讯作者：
Cohn, DH
软骨寡聚基质蛋白（COMP）基因的三核苷酸扩增突变
影响因子：
3.5
作者：
Délot, E;King, LM;Cohn, DH
通讯作者：
Cohn, DH
影响因子：
5.2
作者：
Kennedy, J;Jackson, G;Ramsden, S;Taylor, J;Newman, W;Wright, MJ;Donnai, D;Elles, R;Briggs, MD
通讯作者：
Briggs, MD