PDF(Pubmed)
Abstract：
Pseudoachondroplasia (PSACH) is a rare, dominant genetic disorder affecting bone and cartilage development, characterized by short-limb short stature, brachydactyly, loose joints, joint stiffness, and pain. The disorder is caused by mutations in the COMP gene, which encodes a protein that plays a role in the formation of collagen fibers. In this study, we present the clinical and genetic characteristics of PSACH in two Chinese families. Whole-exome sequencing (WES) analysis revealed two novel missense variants in the COMP gene: NM_000095.3: c.1319G>T (p.G440V, maternal) and NM_000095.3: c.1304A>T (p.D435V, paternal-mosaic). Strikingly, both the G440V and D435V mutations were located in the same T3 repeat motif and exhibited the potential to form hydrogen bonds with each other. Upon further analysis using Missense3D and PyMOL, we ascertained that these mutations showed the propensity to disrupt the protein structure of COMP, thus hampering its functioning. Our findings expand the existing knowledge of the genetic etiology underlying PSACH. The identification of new variants in the COMP gene can broaden the range of mutations linked with the condition. This information can contribute to the diagnosis and genetic counseling of patients with PSACH.
摘要：
假性软骨发育不全（PSACH）是一种罕见的，影响骨和软骨发育的显性遗传病，以身材矮小为特征，Brachydactyly,松动接头,接头刚度,和痛苦。这种疾病是由COMP基因突变引起的，它编码一种在胶原纤维形成中起作用的蛋白质。在这项研究中,我们介绍了两个中国家庭中PSACH的临床和遗传特征。全外显子组测序（WES）分析揭示了COMP基因中的两个新的错义变体：NM_000095.3：c.1319G>T（p。G440V,母体）和NM_000095.3：c.1304A>T（p。D435V,父系马赛克）。引人注目的是，G440V和D435V突变均位于相同的T3重复基序中,并表现出彼此形成氢键的潜力.在使用Missense3D和PyMOL进行进一步分析后，我们确定这些突变显示出破坏COMP蛋白质结构的倾向，从而阻碍了它的运作。我们的发现扩展了PSACH遗传病因的现有知识。COMP基因中新变体的鉴定可以扩大与病症相关的突变的范围。这些信息有助于PSACH患者的诊断和遗传咨询。
