Bregvadze Kakha, Sukhiashvili Anastasia, Lartsuliani Megi, Melikidze Elene, Tkemaladze Tinatin
Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia.
Department of Pediatrics, Givi Zhvania Pediatric Academic Clinic, Tbilisi State Medical University, Tbilisi, Georgia.
SAGE Open Med Case Rep. 2024 Aug 31;12:2050313X241277123. doi: 10.1177/2050313X241277123. eCollection 2024.
The cohesin protein complex plays a vital role in various cellular processes such as sister chromatid cohesion, chromosome condensation, DNA repair, and transcriptional regulation. It is constituted by SMC1, SMC3, RAD21, STAG1/STAG2 subunits, and several regulatory proteins. Pathogenic variants in these components cause cohesinopathies, with common clinical features including facial dysmorphism, delayed growth, developmental delay, and limb anomalies. Pathogenic variants in the contribute to an emerging syndromic developmental disorder with only 21 reported cases in the literature. We describe a 3-year-old girl presenting with congenital bilateral clubfoot and unilateral microphthalmia-clinical manifestations not previously reported in the literature. Whole exome sequencing revealed a novel nonsense variant (c.1183C>T, p.(Arg395*)) in the , expanding the clinical and molecular spectrum of -related cohesinopathy. This patient's unique phenotype highlights the clinical diversity within cohesinopathies, emphasizing their relevance in cases of developmental delay and dysmorphic features. Further studies, including genotype-phenotype correlation analyses and functional investigations, are essential for enhancing our understanding of -related cohesinopathy.
黏连蛋白复合体在多种细胞过程中发挥着至关重要的作用，如姐妹染色单体黏连、染色体浓缩、DNA修复和转录调控。它由SMC1、SMC3、RAD21、STAG1/STAG2亚基以及几种调节蛋白组成。这些成分中的致病变异会导致黏连蛋白病，常见的临床特征包括面部畸形、生长迟缓、发育迟缓以及肢体异常。[此处原文缺失具体基因名称]中的致病变异导致一种新出现的综合征性发育障碍，文献中仅报道了21例病例。我们描述了一名3岁女孩，她患有先天性双侧马蹄内翻足和单侧小眼症——这些临床表现此前在文献中未曾报道。全外显子组测序在[此处原文缺失具体基因名称]中发现了一个新的无义变异（c.1183C>T，p.(Arg395*)），扩展了与[此处原文缺失具体基因名称]相关的黏连蛋白病的临床和分子谱。该患者独特的表型突出了黏连蛋白病的临床多样性，强调了它们在发育迟缓和畸形特征病例中的相关性。进一步的研究，包括基因型-表型相关性分析和功能研究，对于增进我们对与[此处原文缺失具体基因名称]相关的黏连蛋白病的理解至关重要。
