title: Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6.
abstract: We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. thaddeus_dryja@meei.harvard.edu
authors.forename: Thaddeus P
authors.initials: TP
authors.lastname: Dryja
authors.forename: Terri L
authors.initials: TL
authors.lastname: McGee
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Berson
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sandberg
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Alexander
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Derlacki
authors.forename: Aruna S
authors.initials: AS
authors.lastname: Rajagopalan
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D015350:Contrast Sensitivity / Q000502:physiology; D017931:DNA Primers; D004596:Electroretinography; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009755:Night Blindness / Q000235:genetics*; D010375:Pedigree; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D017422:Sequence Analysis, DNA; D014792:Visual Acuity / Q000502:physiology
chemical_list: D017931:DNA Primers; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6