# Expanding TBCE-related phenotype—novel variant causing rigid spine, eosinophilia, neutropenia, and nocturnal hypoxemia

## TL;DR

This paper reports a new TBCE gene variant and expands the known symptoms it causes, including rigid spine and blood-related issues.

## Contribution

The study identifies a novel TBCE variant and describes a milder, distinct clinical phenotype with specific symptoms.

## Key findings

- Homozygous carriers of the c.100 + 1G > A variant show milder symptoms without calcium-phosphate or CNS issues.
- Patients exhibit rigid spine, eosinophilia, neutropenia, and nocturnal hypoxemia.
- The variant is primarily found in Central-Eastern European populations, suggesting a founder effect.

## 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.

The online version contains supplementary material available at 10.1007/s13353-024-00894-9.