# A Novel Mutation in DDR2 Associated with Warburg-Cinotti Syndrome in a Neonate

## TL;DR

A new DDR2 gene mutation is linked to Warburg-Cinotti Syndrome in a newborn, showing unique symptoms and offering insights for diagnosis and treatment.

## Contribution

The study identifies a novel DDR2 mutation and its impact on the p38 MAPK pathway in neonatal Warburg-Cinotti Syndrome.

## Key findings

- A novel DDR2 mutation (c.431A>G, p.Asn144Ser) was found in a neonate with Warburg-Cinotti Syndrome.
- The mutation was maternally inherited and caused failure to activate the p38 MAPK pathway in vitro.
- The patient exhibited respiratory distress due to choanal abnormalities, expanding the known phenotypic spectrum.

## Abstract

Warburg-Cinotti syndrome (WCS) is a rare disorder caused by mutations in the DDR2 gene. We report the first neonatal case with a novel WCS variant, aiming to explore its clinical and genetic characteristics. Clinical data were collected and analyzed retrospectively, and whole exome sequencing (WES) was performed for the family. The patient exhibited significant respiratory distress due to choanal abnormalities, unlike previous reports. WES revealed a maternally inherited heterozygous missense mutation in DDR2 (c.431A>G, p.Asn144Ser). In-vitro experiments showed that the mutated DDR2 fails to activate the p38 MAPK pathway. The study suggests that this novel mutation may contribute to the patient’s condition, especially in the neonatal period, and may expand the phenotypic spectrum, providing new references for clinical diagnosis and gene therapy.