Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram.
OBJECTIVE
Congenital stationary night blindness (CSNB) is a group of nonprogressive retinal disorders characterized by impaired night vision that occurs in autosomal dominant, autosomal recessive, or X-linked forms. Autosomal recessive (ar)CSNB seems to be very rare. Mice lacking the metabotropic glutamate receptor 6 (Grm6) have a defect in signal transmission from the photoreceptors to ON-bipolar cells. In the current study, the human orthologue (GRM6) was screened as a likely candidate for arCSNB.


METHODS
arCSNB individuals of five families were screened for mutations in GRM6. Subsequently, they were examined with standard and 15-Hz flicker electroretinography (ERG). These recordings were compared with those of patients with X-linked CSNB1.


RESULTS
Affected individuals in three of five families carried either compound heterozygous or homozygous mutations in GRM6. Strikingly, all of them displayed a distinctive abnormality of the rod pathway signals on scotopic 15-Hz flicker ERG.


CONCLUSIONS
The novel profile identified in this study suggests the existence of more than two rod pathways. The distinctive ERG feature was not observed in patients with X-linked CSNB1 and additional affected individuals with unknown molecular defect. These observations will help to discriminate autosomal recessive from X-linked recessive cases by ERG and molecular genetic analysis.
Zeitz
Christina
C
Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland. zeitz@medgen.unizh.ch
van Genderen
Maria
M
Neidhardt
John
J
Luhmann
Ulrich F O
UF
Hoeben
Frank
F
Forster
Ursula
U
Wycisk
Katharina
K
Mátyás
Gábor
G
Hoyng
Carel B
CB
Riemslag
Frans
F
Meire
Françoise
F
Cremers
Frans P M
FP
Berger
Wolfgang
W
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008027:Light; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009755:Night Blindness / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology*; D014785:Vision, Ocular
D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6