Tourette, Discussion

Neuroligins are an intriguing study target for neuropsychiatric conditions due to their potential role in synapse function and neuron-to-neuron recognition.
Lack of expression of specific neuroligins could affect neuronal interactions within the synaptic network, leading to consequent neuropathology
This family's varied neuropsychiatric phenotypes suggest that mutations in NLGN4 may be associated with a wider clinical spectrum than previously described, including depression, anxiety, and tic disorders.
Their varied pheno-types, all associated with the same mutation, suggest that epigenetic factors play a role in determining presentation.
This also suggests that derangement of core elements of synapse function may be associated with multiple neuropsychiatric conditions.
Gene dosage may be integral to neuroligin function as suggested by the mother's relatively mild symptoms (as compared wth her sons) of learning disorder, anxiety, and depression.
Knowledge of the mother's X-chromosome inactivation status would be valuable in this interpretation, but was unfortunately not available.
This may have important genetic counseling implications, as carrier mothers with mild symptoms may be at risk to have severely affected offspring.