Gene Networks Underlying Convergent and Pleiotropic Phenotypes in a Large and Systematically-Phenotyped Cohort with Heterogeneous Developmental Disorders

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Developmental disorders occur in ∼3% of live births, and exhibit a broad range of abnormalities including: intellectual disability, autism, heart defects, and other neurological and morphological problems. Often, patients are grouped into genetic syndromes which are defined by a specific set of mutations and a common set of abnormalities. However, many mutations are unique to a single patient and many patients present a range of abnormalities which do not fit one of the recognized genetic syndromes, making diagnosis difficult. Using a dataset of 197 patients with systematically described abnormalities, we identified molecular pathways whose disruption was associated with specific abnormalities among many patients. Importantly, patients with mutations in the same pathway often exhibited similar co-morbid symptoms and thus the commonly disrupted pathway appeared responsible for the broad range of shared abnormalities amongst these patients. These findings support the general concept that patients with mutations in distinct genes could be etiologically grouped together through the common pathway that these mutated genes participate in, with a view to improving diagnoses, prognoses and therapeutic outcomes.

Vyšlo v časopise: Gene Networks Underlying Convergent and Pleiotropic Phenotypes in a Large and Systematically-Phenotyped Cohort with Heterogeneous Developmental Disorders. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005012
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005012

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