Abstract
We report three patients with the novel variant c.100 + 1G > A of the TBCE gene and describe the presented clinical phenotype in detail. We also systematically reviewed the literature for clinical similarities and dissimilarities among all known patients with pathogenic TBCE variants. The clinical phenotype observed in patients with pathogenic TBCE variants is broader than previously described. Homozygous carriers of the c.100 + 1G > A variant exhibit a markedly milder clinical course, with no deviations in the calcium-phosphate metabolism and central nervous system pathology in MRI studies. Additionally, two patients manifest highly specific symptoms such as a rigid spine, eosinophilia, neutropenia, and nocturnal hypoxemia. Furthermore, cryptorchidism was observed in male patients. The identification of the pathogenic c.100 + 1G > A variant has thus far been limited to patients of Central-Eastern European descent, suggesting a potential founder mutation in this population.