# The Expression of a Germline Fusion Gene Involving a Protein-Coding and a Long Non-Coding RNA Gene Results in Severe Brain Malformations

## TL;DR

A rare genetic fusion involving a protein-coding gene and a long non-coding RNA gene causes severe brain malformations in a fetus.

## Contribution

First report of a germline fusion between a protein-coding and lncRNA gene resulting in a neomorphic protein linked to severe disease.

## Key findings

- Germline fusion of MN1 and CPMER genes was identified as the cause of severe cerebral abnormalities.
- Expression of C-terminally truncated MN1 proteins was observed, similar to a known gain-of-function syndrome.
- The study highlights the potential role of lncRNA-involved gene fusions in disease-related protein expression.

## Abstract

In the present study, an exceptional germline gene fusion involving the protein-coding MN1 gene and the long non-coding RNA (lncRNA) gene CPMER was detected as the genetic cause of severe cerebral abnormalities with unfavorable prognosis in a male fetus at 14 weeks of gestation. Quantitative and qualitative RNA analyses indicate the expression of C-terminally truncated MN1 proteins. MN1 proteins lacking the C-terminal amino acids have been previously described to cause an ultra-rare syndrome with brain malformations due to a gain-of-function effect. To the best of our knowledge, this is the first study reporting a germline gene fusion of a protein-coding gene and an lncRNA gene linked to a functional, but neomorphic, protein associated with severe phenotypic abnormalities. The results of our study are not only relevant for the genotype–phenotype correlation of MN1 but should especially raise awareness for potentially disease-associated protein expressions in germline gene fusions involving lncRNAs.