# Whole-Exome Sequencing Analysis Identifies Risk Genes in Atlantoaxial Dislocation Patients with Sandwich Fusion

## TL;DR

This study uses whole-exome sequencing to identify risk genes in a rare spinal disorder called sandwich fusion, offering new genetic insights for diagnosis and treatment.

## Contribution

The study identifies novel risk genes and oligogenic effects in a rare spinal disorder using whole-exome sequencing in a Chinese patient cohort.

## Key findings

- Genes like KMT5A, HYDIN, and PCDHB4 were found to have significant genetic variations in patients with sandwich fusion.
- Severe cases showed oligogenic effects involving mutations in genes like MEOX1, linked to spinal severity.
- The findings provide a genetic foundation for understanding and treating sandwich fusion in Klippel-Feil syndrome.

## Abstract

Sandwich fusion of Klippel-Feil syndrome (KFS), which is a rare congenital disorder involving the fusion of cervical vertebrae, poses significant challenges in the diagnosis and treatment of atlantoaxial dislocation (AAD). While the disorder's genetic basis is not well-understood, the rarity of the sandwich fusion makes it difficult to study. Whole-exome sequencing (WES) was conducted on 68 unrelated Chinese patients with sandwich fusion. The study compared their genetic data with a control group of 219 individuals without musculoskeletal disorders. Various analyses, including mutational burden assessments, were employed to identify potential pathogenic genes. The study identified significant genetic variations in patients with sandwich fusion, highlighting genes like KMT5A, HYDIN, and PCDHB4 as potential contributors. Notably, severe cases exhibited oligogenic effects, with mutations in genes like MEOX1 associated with the severity of spinal issues. These findings offer critical insights into the genetic basis of sandwich fusion and provide a foundation for future research and therapeutic development.