The gene that causes rohhad

Overview

Scientists who are now studying ROHHAD previously discovered that mutations in a gene called PHOX2B cause a disorder named CCHS. This discovery allowed for earlier diagnosis, improved treatment, and clinical trials to improve outcomes in CCHS. ROHHAD and CCHS have many overlapping features, so these scientists hope to make a similar discovery in ROHHAD. The contribution of genetic variants to ROHHAD remains unknown right now, but genomic sequencing and other research tools are helping scientists investigate potential genes and biomarkers.

This research project aims to uncover the molecular and genetic mechanisms underlying ROHHAD(NET) syndrome through a multi-disciplinary approach.

Genomic Discovery: The team is conducting whole genome sequencing (WGS) of ROHHAD(NET) family trios using advanced machine-learning tools to detect coding, non-coding variants, and structural variants.

Neuroimaging and Biomarkers: Using a novel segmentation protocol, the team is measuring hypothalamic volumes from patient MRI scans and correlating these with clinical severity. Blood samples are being analysed for biomarkers, such as specific antibodies (anti-ZSCAN1) and hypothalamic hormones (neuropeptides) that regulate hunger, satiety, and fluid balance. These may support earlier diagnosis and help predict disease progression.

How can you participate?

ROHHAD(NET) families can contribute to this research through genetic testing, MRI data sharing, or donating blood samples for biomarker analysis. If you are interested in participating or would like more information, please contact the research team via m.dattani@ucl.ac.uk.

Meet the Team

Lead Researcher: Prof. Mehul Dattani, MBBS DCH FRCPCH FRCP MD

Research Team: Dr. Federica Buonocore, PhD; Dr. Manuela Cerbone, MD, PhD

Institutions: UCL Great Ormond Street Institute of Child Health, Great Ormond Street Hospital

Professor Dattani and his team at the UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) have extensive clinical and research experience in hypothalamic disorders and complex genetic analysis. We are leading a comprehensive project to investigate the molecular and genetic mechanisms behind ROHHAD(NET) syndrome. Using whole genome sequencing, advanced neuroimaging, and biomarker analysis, the team aims to improve diagnosis and develop targeted treatments.

The ultimate goal is to enhance both life span and quality of life for children affected by ROHHAD(NET), while supporting families and healthcare professionals with better tools and understanding.