Lessel-Kreienkamp Syndrome (AGO2)

Lessel-Kreienkamp Syndrome (AGO2) is an Argonaute-related neurodevelopmental disorder characterized by developmental delay or intellectual disability, severe speech impairment, hypotonia, motor abnormalities and variable epilepsy, behavioral features, feeding problems and distinctive facial characteristics.

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Genetics

Usually caused by de novo heterozygous missense or in-frame variants in AGO2. Pathogenic alleles affect conserved regions required for RNA binding, target recognition or catalytic and conformational transitions.

Molecular Mechanism

AGO2 is the catalytic core of the microRNA-induced silencing complex. Disease variants disturb microRNA loading, target dwell time, cleavage or recycling and can cause both loss of intended silencing and aberrant targeting; the mechanism is not equivalent to simple haploinsufficiency.

Therapy

Treatment is supportive and focuses on communication, development, motor function, feeding, behavior, sleep and epilepsy. No molecular therapy is established; allele-specific functional analysis is essential before considering silencing or replacement strategies.

CCP Activity

CCP has developed and has been characterizing an AGO2 disease model. We design and plan neurobehavioral and systemic phenotyping.

Mouse Models Mouse Models & Gene Cards

Mouse Models	Gene Cards
TBD	TBD