Natalie J. Abtan
Scientific Writing – Assignment III – Instructor: Dr. Jeffrey Toney
GNB5 Mutation Causes a Novel Neuropsychiatric Disorder Featuring Attention Deficit
Hyperactivity Disorder, Severely Impaired Language Development and Normal Cognition
Neuropsychiatry amalgamates the disciplines of psychiatry and neurology to establish
connections between mental disorders and disabilities with their possible genetic configurations.
Neuropsychiatry is a branch of medicine that addresses mental disorders that are attributed to
diseases of the nervous system. Although the fields of psychiatry and neurology are
predominately practiced separately, there are great associations between the genetic components
in the brain and the subsequent behavior recognized as a result of its genetic baseline. As
neuropsychiatric disorders become more common, many studies have been focused on relating
certain disorders and disabilities to regions of the brain lacking important gene expression, or
containing genes that do not function properly. Even with the tremendous advances science has
achieved in the understanding of the genetic components that could be contributing to
neuropsychiatric conditions, linking the specific disorders and their associated behaviors to
molecular compositions or gene deficiencies has been more challenging.
One particular family of gene regulators, associated with G protein receptors known as
GPCR, have been recognized as playing prominent roles in treating neuropsychiatric diseases.
Notably, pharmacological modulation of signaling efficacy at GPCR has been among the most
successful strategies for controlling the symptoms of several mental conditions.1 Activation of
heterotrimeric guanine nucleotide binding proteins regulates GPCR transmission. When the body
is in its resting metabolic state, GDP-bound Gα is tightly bound to the Gβγ heterodimer. Upon
binding of GPCR’s to their ligands, GDP is exchanged for GTP and the heterodimer dissociates
such that each of its components can initiate a series of signaling cascades that mediate the net
biological effect of the ligand.2 The intensity of GPCR signaling is controlled by regulators of G
protein signaling known as RGS proteins. RGS proteins are responsible for terminating the
signaling initiated by the GPCR’s. RGS proteins also act to limit signaling, preventing
uncontrolled G protein signaling in the absence of GPCR activation.3 GPCR signaling belongs to
members of the R7 subfamily of RGS proteins that include RGS6, RGS7, RGS9 and RGS11.
Collectively, R7 RGS proteins have been implicated in learning, motor control, and vision by
controlling several neurotransmitter systems.4
A key relevant association in the R7 RGS proteins is their connection with Gβ5. Gβ5, an
