IFIH1基因编码黑色素瘤分化相关基因5(MDA5),并与Aicardi-Goutières综合征(AGS)相关,单例-默顿综合征(SMS),和其他自身免疫性疾病。单个基因的功能变化如何导致许多不同的表型的机制仍然未知。此外,对于这些不同的表型是否代表相同的疾病连续性或突变特异性疾病,存在显著争议.这里,我们描述了一个新的c.1465G>T的患者的病例(p.Ala489Ser)IFIH1基因的突变。病人出现了痉挛性截瘫,肌张力障碍,精神运动性迟钝,关节畸形,颅内钙化,牙列异常,特征性的面部特征,淋巴结病,和自身免疫。他的表型似乎代表AGS和SMS表型的重叠。患者还经历了原因不明的全血细胞减少症,提示血液系统可能受到IFIH1基因功能获得突变的影响。总之,我们提供了进一步的证据,表明SMS和AGS在IFIH1基因发生功能获得性突变后表现出相同的疾病谱.我们的数据突出了这些条件的遗传异质性,并扩展了我们对IFIH1功能获得突变产生的差异表型的认识。
The
IFIH1 gene encodes melanoma differentiation-associated gene 5 (MDA5) and has been associated with Aicardi-Goutières syndrome (AGS), Singleton-Merten syndrome (SMS), and other autoimmune diseases. The mechanisms responsible for how a functional change in a single gene can cause so many different phenotypes remain unknown. Moreover, there is significant controversy as to whether these distinct phenotypes represent the same disease continuum or mutation-specific disorders. Here, we describe the
case of a patient with a novel c.1465G > T (p.Ala489Ser) mutation in the
IFIH1 gene. The patient presented with spastic paraplegia, dystonia, psychomotor retardation, joint deformities, intracranial calcification, abnormal dentition, characteristic facial features, lymphadenopathy, and autoimmunity. His phenotype appeared to represent an overlap of the phenotypes for AGS and SMS. The patient also experienced unexplained pancytopenia, suggesting that the hemic system may have been affected by a gain-of-function mutation in the
IFIH1 gene. In summary, we provide further evidence that SMS and AGS exhibit the same disease spectrum following a gain-of-function mutation in the
IFIH1 gene. Our data highlight the genetic heterogeneity of these conditions and expand our knowledge of differential phenotypes created by
IFIH1 gain-of-function mutation.