STIM1中的功能增益(GOF)突变是肾小管聚集肌病和Stormorken综合征(TAM/STRMK)的原因,一种以肌肉无力为特征的临床重叠多系统疾病,瞳孔缩小,血小板减少症,脾功能减退,鱼鳞病,诵读困难,身材矮小。已经报道了几种突变是该疾病的原因。在这里,我们描述了由于新的L303PSTIM1突变而患有TAM/STRMK的患者,他们不仅表现出TAM/STRMK的临床表现特征,而且从小就表现出与呼吸道感染的免疫参与,慢性咳嗽和慢性支气管扩张。尽管看似正常的主要免疫学参数,与健康供体相比,免疫细胞在钙信号中显示GOF。免疫细胞中的钙通量失调可能是我们患者免疫参与的原因。患者的母亲携带突变,但未表现出TAM/STRMK,表现出突变的不完全外显。需要更多的病例和证据来阐明STIM1在免疫系统失调和肌病中的双重作用。
Gain-of-function (GOF) mutations in STIM1 are responsible for tubular aggregate myopathy and Stormorken syndrome (TAM/STRMK), a clinically overlapping multisystemic disease characterised by muscle weakness, miosis, thrombocytopaenia, hyposplenism, ichthyosis, dyslexia, and short stature. Several mutations have been reported as responsible for the disease. Herein, we describe a patient with TAM/STRMK due to a novel L303P STIM1 mutation, who not only presented clinical manifestations characteristic of TAM/STRMK but also manifested immunological involvement with respiratory infections since childhood, with chronic cough and chronic bronchiectasis. Despite the seemingly normal main immunological parameters, immune cells revealed GOF in calcium signalling compared with healthy donors. The calcium flux dysregulation in the immune cells could be responsible for our patient\'s immune involvement. The patient\'s mother carried the mutation but did not exhibit TAM/STRMK, manifesting an incomplete penetrance of the mutation. More cases and evidence are necessary to clarify the dual role of STIM1 in immune system dysregulation and myopathy.