PDF(Pubmed)
Abstract：
The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands\' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14-15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands\' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14-15 deletion could cause CMS.
摘要：
编码不对称乙酰胆碱酯酶（COLQ）的胶原样尾亚基的基因负责乙酰胆碱酯酶的三股胶原的转录，它附着在神经肌肉接头的终板上。COLQ基因突变以常染色体隐性遗传方式遗传，可导致V型先天性肌无力综合征（CMS），表现为出生时或出生后不久肌肉力量下降，呼吸衰竭,受限的眼球运动，下垂的眼睑，吞咽困难。在这里，我们报告了两个无关的CMS儿童的COLQ中的三个变体。内含子变体（c.3931G>A）和新的错义变体（p。Q381P）在一个13个月大的男孩中被鉴定为复合杂合，父母是每个人的携带者。在一个12岁的男孩中以纯合状态发现了包括外显子14和15的基因内缺失。我们研究了COLQ和AChE基因在先证者家族中的相对表达，进行了三维蛋白质结构分析，并分析了错义突变c.1142A>C的保守性（p。Q381P）。发现剪接突变c.393+1G>A影响COLQ外显子5的正常剪接,导致27-bp缺失。错义突变c.1142A>C（p。Q381P）在不同物种中位于保守位置。我们发现COLQ外显子14-15的纯合缺失导致241bp的缺失，这减少了氨基酸的数量并导致了移码翻译。先证者的COLQ表达显著低于先证者的父母和兄弟姐妹，而AChE表达显著增高。此外，发现突变导致蛋白质预测的三维结构存在显着差异。剪接突变c.393+1G>A,错义突变c.1A>C(p.Q381P),和COLQ外显子14-15缺失可能导致CMS。
