Familial Autonomic Ganglionopathy Caused by Rare Genetic Variants.

Objective: To determine the molecular basis of a new monogenetic recessive disorder that results in familial autonomic ganglionopathy with diffuse autonomic failure.

Methods: Two adult siblings from one family (I-4 and I-5) and another participant from a second family (II-3) presented with severe neurogenic orthostatic hypotension (nOH), small nonreactive pupils, and constipation. All 3 affected members had low norepinephrine levels and diffuse panautonomic failure.

Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium.

Fibroblasts are a diverse cell type and display clear topographic differentiation and positional memory. In a screen for fibroblast specific markers we have characterized four monoclonal antibodies to endosialin (TEM1/CD248). Previous studies have reported that endosialin is a tumour endothelium marker and is localized intracellularly.