运输蛋白颗粒(TRAPP)复合物是一种多亚基蛋白复合物,可作为参与细胞内运输的束缚因子发挥作用。TRAPPC11,这个复合物的关键亚基,与导致一系列疾病谱的致病变异有关,从四肢带型肌营养不良症(LGMD)到肌肉疾病的发育障碍,运动障碍和全球发育迟缓(GDD)/智力残疾(ID),甚至是先天性肌营养不良(CMD)。我们回顾了所有报告的TRAPPC11病个体的表型,包括另外一名在TRAPPC11中具有新的复合杂合错义变体的墨西哥患者(c.751T>C和c.1058C>G),仅限于拉丁裔人口。在这54例患者中,肌营养不良症状很常见(早发性肌无力,血清肌酸激酶水平升高,和肌肉活检中的营养不良变化)。它们呈现两种主要的表型,一个有或没有GDD/ID的缓慢进行性LGMD(n=12),另一个以身材矮小为特征的系统性参与,GDD/ID,小头畸形,低张力,糟糕的演讲,癫痫发作,脑萎缩,小脑异常,运动障碍,脊柱侧弯,肝病,和白内障(n=42)。在其中6个CMD被鉴定。阻塞性脑积水,小脑后囊肿,在本文报道的个体中发现的马蹄内翻足在TRAPPC11缺乏症中没有描述。和以前的病人一样,我们患者的膜运输分析显示内质网-高尔基体转运异常缺陷以及LAMP2和ICAM-1糖蛋白表达降低.这支持先前的说法,即TRAPPC11病实际上是患有肌营养不良的先天性糖基化疾病(CDG)。
The trafficking protein particle (TRAPP) complex is a multisubunit protein complex that functions as a tethering factor involved in intracellular trafficking. TRAPPC11, a crucial subunit of this complex, is associated with pathogenic variants that cause a spectrum of disease, which can range from a limb girdle muscular dystrophy (LGMD) to developmental disability with muscle disease, movement disorder and global developmental delay (GDD)/intellectual disability (ID), or even a congenital muscular dystrophy (CMD). We reviewed the phenotype of all reported individuals with TRAPPC11-opathies, including an additional Mexican patient with novel compound heterozygous missense variants in TRAPPC11 (c.751 T > C and c.1058C > G), restricted to the Latino population. In these 54 patients muscular dystrophy signs are common (early onset muscle weakness, increased serum creatine kinase levels, and dystrophic changes in muscle biopsy). They present two main phenotypes, one with a slowly progressive LGMD with or without GDD/ID (n = 12), and another with systemic involvement characterized by short stature, GDD/ID, microcephaly, hypotonia, poor speech, seizures, cerebral atrophy, cerebellar abnormalities, movement disorder, scoliosis, liver disease, and cataracts (n = 42). In 6 of them CMD was identified. Obstructive hydrocephaly, retrocerebellar cyst, and talipes equinovarus found in the individual reported here has not been described in TRAPPC11 deficiency. As in previous patients, membrane trafficking assays in our patient showed defective abnormal endoplasmic reticulum-Golgi transport as well as decreased expression of LAMP2, and ICAM-1 glycoproteins. This supports previous statements that TRAPPC11-opathies are in fact a congenital disorder of glycosylation (CDG) with muscular dystrophy.