SKI pathogenic variations are associated with Shprintzen-Goldberg Syndrome (SGS), a rare systemic connective tissue disorder characterized by craniofacial, skeletal and cardiovascular features. So far, the clinical description, including intellectual disability, has been relatively homogeneous, and the known pathogenic variations were located in two different hotspots of the SKI gene. In the course of diagnosing Marfan syndrome and related disorders, we identified nine sporadic probands (aged 2-47 years) carrying three different likely pathogenic or pathogenic variants in the SKI gene affecting the same amino acid (Thr180). Seven of these molecular events were confirmed de novo. All probands displayed a milder morphological phenotype with a marfanoid habitus that did not initially lead to a clinical diagnosis of SGS. Only three of them had learning disorders, and none had intellectual disability. Six out of nine presented thoracic aortic aneurysm, which led to preventive surgery in the oldest case. This report extends the phenotypic spectrum of variants identified in the SKI gene. We describe a new mutational hotspot associated with a marfanoid syndrome with no intellectual disability. Cardiovascular involvement was confirmed in a significant number of cases, highlighting the importance of accurately diagnosing SGS and ensuring appropriate medical treatment and follow-up.

中文翻译：

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在MFS / TAA分子诊断的背景下，SKI基因中出现了一个新的突变热点。

SKI的致病变异与Shprintzen-Goldberg综合征（SGS）有关，后者是一种罕见的全身性结缔组织疾病，其特征是颅面，骨骼和心血管特征。到目前为止，包括智力障碍在内的临床描述相对均一，已知的病原变异位于SKI基因的两个不同热点。在诊断马凡氏综合症和相关疾病的过程中，我们确定了9个散发先证者（2-47岁），他们在SKI基因中携带三种影响相同氨基酸（Thr180）的不同致病或致病变异。这些分子事件中有七个是从头证实的。所有先证者均表现出较温和的形态学表现型，并具有类迷蝶状的习性，最初并未导致SGS的临床诊断。他们中只有三人患有学习障碍，没有人有智力障碍。九分之六的患者表现为胸主动脉瘤，这导致了最老的情况下的预防性手术。该报告扩展了在SKI基因中鉴定出的变异的表型谱。我们描述了一种新的与马凡尼德综合征相关的突变热点，无智力障碍。在很多情况下都确认了心血管受累，突出了准确诊断SGS并确保适当的医学治疗和随访的重要性。我们描述了一种新的与马凡尼德综合征相关的突变热点，无智力障碍。在很多情况下都确认了心血管受累，突出了准确诊断SGS并确保适当的医学治疗和随访的重要性。我们描述了一种新的与马凡尼德综合征相关的突变热点，无智力障碍。在很多情况下都确认了心血管受累，突出了准确诊断SGS并确保适当的医学治疗和随访的重要性。