Pathogenic mechanisms in rare deseases: the case of PHOX2B in CCHS

Challenges: Rare Diseases

CSIC White books:

• Rare diseases (Challenge 4; CSIC white book vol.4)
• Understanding mental disorders (Challenge 6; CSIC white book vol.5)

PI: Javier Oroz

• Miguel Ángel Treviño
• Douglas V. Laurents
• David Pantoja-Uceda
• Rosa Antón García

Polyalanine expansions in PHOX2B are responsible for the develoment of the rare disease CCHS. The pathogenic mechanisms that trigger disease are fully unknown. We aim to understand the structural basis of toxic poly-alanine expansions in PHOX2B as a model to understand the principles of pathogenicity for trinucleotide repeat expansions. We employ advanced NMR spectroscopy methods for the structural analysis of PHOX2B considering its extremely low sequence complexity.

In the figure, putative domain architecture in PHOX2B. Stars indicate proposed amyloidogenic segments.

Collaborators

Financing

• Spanish Ondine Association (2019)
• Mexican Ondine Association (2020)