Analysis of disease genes for skeletal dysplasias

为了建立骨骼发育不良、骨和软骨遗传疾病的DNA诊断体系，并深入了解其发病机制，我对骨骼发育不良进行了遗传分析，得到以下结果：1。直接测序并不总是可靠的。由于PCR引物和扩增子之间的序列相同，可以发生等位基因特异性PCR扩增。我们在x连锁显性点状软骨发育不良中发现了3个新的EBP突变，并发现扭曲的x染色体失活导致家族内表型变异。(1)我们在假性软骨发育不全和多发性骨骺发育不良（MED）中发现了9个新的COMP突变，并发现了基因型-表型相关性。(2)首次发现Torrance型脊椎病是COL2A1突变所致。(3)我们在以下疾病中发现了新的突变：(4)COL2A - 1在软骨发育不良、先天性脊柱骨骺发育不良、Kniest发育不良、Stickler综合征和迟发性脊柱骨骺发育不良中。(5) MED中的MAIN3和COL9A3。(6)软骨毛中的RMRP。(7)TGFB1在Camurati-Engelmann病中的作用。(8) Shwachman-Diamond综合征的SBDS。我们发现携带COMP突变的假性软骨发育不全和多发性骨骺发育不良患者循环COMP减少。

To establish a system for DNA diagnosis of skeletal dysplasias, genetic disorders of bone and cartilage, and gain insight for their pathogenesis, I performed genetic analysis of skeletal dysplasias and obtained the following results.1.Direct sequencing is not always reliable. Allele specific PCR amplification could occur due to sequence identity between a PCR primer and an amplicon.2.We identified 3 novel EBP mutations in X-linked dominant chondrodysplasia punctata and found skewed X-chromosome inactivation causes intra-familial phenotypic variation.(1)We identified 9 novel COMP mutations in pseudoachondroplasia and MED (multiple epiphyseal dysplasia) and genotype-phenotype association.(2)We identified for the first time that platyspondylic skeletal dysplasia, Torrance type is caused by COL2A1 mutation.(3)We found novel mutations in the following disease:(4)COL2A 1 in hypochondrogenesis、 spondyloepiphyseal dysplasia congenita、 Kniest dysplasia、Stickler syndrome and spondyloepiphyseal dysplasia tarda.(5)MAIN3 and COL9A3 in MED.(6)RMRP in Cartilage-Hair ].(7)TGFB1 in Camurati-Engelmann disease.(8)SBDS in Shwachman-Diamond syndrome.3.We found circulating COMP is decreased in pseudoachondroplasia and multiple epiphyseal dysplasia patients carrying COMP mutations.