Stormorken Syndrome Caused by STIM1 H109R Mutation

Stormorken Syndrome is an extremely rare disease with autosomal dominant inheritance, has a variable degree of multisystemic signs, including muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, short stature, and dyslexia. we identified the c.326A>G mutation in a STIM1 allele (p.H109R) only in the child and not in the unaffected parents. The mutation was predicted to be harmful by protein function prediction software. We found mutations associated with TAM/STRMK upon consulting HGMD database. The variant located in the EF-hand supposedly led to constitutive STIM1 unfolding and oligomerization. The affected amino acids in this residue was evolutionarily conserved, which indicated an important functional role. The 3D structures of STIM1 and mutated proteins were constructed in SWISS-MODEL. No differences in STIM1 expression levels were observed between our case and healthy controls.

Stormorken 综合征是一种极为罕见的常染色体显性遗传性疾病，其多系统症状程度不一，包括肌肉无力、瞳孔缩小、血小板减少、脾功能低下、鱼鳞病、侏儒症以及阅读障碍。我们在患儿的 STIM1 基因型中识别出 c.326A> G 突变（p.H109R），而在无影响的父母中并未发现该突变。蛋白质功能预测软件预测该突变可能具有害性。通过查阅 HGMD 数据库，我们发现与 TAM/STRMK 相关的突变。位于 EF 手的变异可能导致了 STIM1 的构成性展开和寡聚化。在此残基处的受影响氨基酸在进化过程中保持保守，这表明其具有重要的功能作用。我们利用 SWISS-MODEL 构建了 STIM1 和突变蛋白的 3D 结构。在我们的病例与健康对照者之间，未观察到 STIM1 表达水平的差异。