Genetic analysis of skeletal dysplasias

我对骨骼发育不良、骨和软骨遗传疾病进行了遗传分析，得到如下结果：1。我发现X型胶原蛋白基因突变（col10a1）在一个患有脊柱干骺端发育不良的病人。这是在这种情况下鉴定突变的第一份报告。在Schmid干骺端软骨发育不良患者中已经报道了一些col10a1突变，但它们都位于X型胶原的c端球状结构域。我在n端球状结构域中发现了两个新的错义突变。n端结构域在X型胶原的形成中也起着重要作用。我在假性软骨发育不全（PAP）中发现了8个COMP（软骨寡聚基质蛋白）基因突变；其中3篇是常写的，5篇是小说。通过对突变的分析，我发现了基因型-表现型的相关性。在PAP中发现了COMP基因突变；然而，PAP的临床和遗传异质性已被报道，表明可能存在第二个PAP基因。我发现1例PAP患者在11号染色体长臂出现了新发间质缺失[del(11)(q22.2)]。使用荧光原位杂交（FISH）估计缺失的大小约为7 mb。在患者中被破坏的第二个PAP基因可能位于缺失的断点上。我在一个患有多发性骨骺发育不良的病人身上发现了一种新的COMP突变。

I performed the genetic analysis of skeletal dysplasias, genetic disorders of bone and cartilage, and obtained the following results.1. I found a mutation of type X collagene gene (COL 10A1) in a patient with spondylometaphyseal dysplasia. This is the first report of identification of mutation in this condition.2. Several mut : tions of the COL 10A1 have been reported in patients with Schmid metaphyseal cnondrodysplasia, but all of them are situated in the C-terminal globular domain of the type X collagen. I identified two novel missense mutations in the N-terminal globular domain. The N-terminal domain also plays an important role in formation of type X collagen.3. I identified 8 mutations of the COMP(cartilage oligomeric matrix protein)gene in pseudoachondroplasia (PAP) ; three of them were reccurrent and five novel. Through the analysis of mutations, I found a genotype-phenotype correlation.4. Mutation of the COMP gene has been identified in PAP ; however, clinical and genetic heterogeity has been reported in PAP, indicating a possible presence of the second PAP gene. I have found a patient with a PAP who had a de novo interstitial deletion in the long arm of chromosome 11 [del(11)(q22.2)]. The size of the deletion was estimated approximately 7-Mb using fluorescence in situ hybridization (FISH). The second PAP gene, which was disrupted in the patient may be located at the breakpoints of the deletion.5. I identified a novel COMP mutation in a patient with multiple epiphyseal dysplasia.