Genetic analysis of skeletal dysplasias

我进行了骨骼发育不良的遗传分析，骨和软骨的遗传疾病，并获得了以下结果。1.我在一个腰椎滑脱发育不良的患者中发现了X型胶原基因（COL 10A 1）的突变。这是第一次在这种情况下鉴定突变的报道.几个哑巴：在Schmid干骺端软骨发育不良患者中也有COL 10A 1的表达，但均位于X型胶原的C端球状结构域。我发现了两个新的错义突变的N-末端球状域。N端结构域在X型胶原的形成中也起重要作用.我确定了8个突变的COMP（软骨寡聚基质蛋白）基因在假性软骨发育不全（PAP），其中三个复发和五个新的。通过对突变的分析，发现了基因型与表型的相关性. COMP基因的突变已被确定在PAP，然而，临床和遗传异质性已报告在PAP，表明可能存在的第二PAP基因。我发现一名PAP患者在11号染色体长臂[del（11）（q22.2）]中出现从头间质性缺失。使用荧光原位杂交（FISH）估计缺失的大小约为7-Mb。第二个PAP基因在患者中被破坏，可能位于缺失的断点处。我在一例多发性骨骺发育不良患者中发现了一种新的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.