Defining the progeria phenome

• Published in: Aging (Albany, NY.) Vol. 16; no. 3; pp. 2026 - 2046
• Main Authors: Worm, Cecilie, Schambye, Maya Elena Ramirez, Mkrtchyan, Garik V, Veviorskiy, Alexander, Shneyderman, Anastasia, Ozerov, Ivan V, Zhavoronkov, Alex, Bakula, Daniela, Scheibye-Knudsen, Morten
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 09.02.2024
• Subjects: Aging; Aging, Premature - genetics; Cockayne Syndrome; Growth Disorders - complications; Humans; Phenotype; Progeria - genetics; Progeria - pathology; Research Paper; progeria; phenome; aging; premature aging; clinical phenotype
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.205537

Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. To accommodate the challenge, we compiled a list of known progeroid syndromes and calculated the mean prevalence of their associated phenotypes, defining what we term the 'progeria phenome'. The data were used to train a support vector machine that is available at https://www.mitodb.com and able to classify progerias based on phenotypes. Furthermore, this allowed us to investigate the correlation of progeroid syndromes and syndromes with various pathogenesis using hierarchical clustering algorithms and disease networks. We detected that ataxia-telangiectasia like disorder 2, spastic paraplegia 49 and Meier-Gorlin syndrome display strong association to progeroid syndromes, thereby implying that the syndromes are previously unrecognized progerias. In conclusion, our study has provided tools to evaluate the likelihood of a syndrome or patient being progeroid. This is a considerable step forward in our understanding of what constitutes a premature aging disorder and how to diagnose them.