Prader-Willi Syndrome

Prader-Willi Syndrome is a multisystem imprinting disorder with severe neonatal hypotonia and feeding difficulty followed by hyperphagia, obesity risk, short stature, hypogonadism, sleep abnormalities, endocrine dysfunction, mild-to-moderate cognitive impairment and a characteristic behavioral phenotype. More info

SHOW MOUSE MODELS

Genetics

Caused by loss of expression of paternally active genes in chromosome 15q11.2-q13, most often through a paternal deletion, maternal uniparental disomy or an imprinting defect. The critical region includes SNORD116 and multiple coding and noncoding transcripts.

Molecular Mechanism

Loss of the paternal gene network disrupts hypothalamic development and circuits controlling satiety, endocrine axes, sleep, autonomic regulation and energy balance. SNORD116 is central, but the phenotype reflects a dosage-sensitive multigene and noncoding-RNA disorder.

Therapy

Management requires strict environmental control of food access, nutritional planning, growth hormone, treatment of hypogonadism and other endocrine deficits, sleep and respiratory care, and behavioral support. No therapy restores the missing paternal locus; hyperphagia-directed drugs remain under investigation.

CCP Activity

CCP uses complementary PWS-region deletion models to characterize locus-specific mechanisms. Longitudinal phenotyping, direct-RNA and transcriptomic analyses, and tissue metabolic profiling in order to find new possible therapeutic intervention targets.