DNA diagnostics in Congenital Stationary Nightblindness (CSNB).

Congenital stationary night blindness (CSNB) is a group of retinal disorders
that causes variable problems at night, variable reduced visual acuity and
often refractive errors. CSNB is caused by defective transfer of signals from
photoreceptors (rods and cones) to bipolar cells, the junction cells of the
retina. Diagnoses are based on clinical symptoms and the Electroretinogram
(ERG), a method that records the electrical activity of the retina during the
exposure to variable light intensities. The distinctive ERG of a CSNB patient
shows the dysfunction of the signal transfer to bipolar cells. Two types of
CSNB can be distinguished: the *complete* and *incomplete* form, also known as
CSNB1 and CSNB2 respectively. CSNB1 is characterized by the complete absence of
rod pathway function, for CSNB2 both rod and cone pathways functions are
impaired. The clinical symptoms of the two groups are clearly different.

Mutations in the NYX gene cause CSNB1 and mutations in the CACNA1F gene cause
CSNB2. These X-linked genes were identified approximately 10 years ago.
Recently, four autosomal recessive genes have been identified that can cause
CSNB. Mutations in the GRM6 gene or the TRPM1 gene cause CSNB1 and mutations in
the CABP4 gene or the CACNA2D4 gene cause CSNB2. It is probable that there are
more undiscovered genes that can cause CSNB when a mutation is present.

CSNB is a congenital disorder and visual functions change little during live.
CSNB patients usually have impaired visual acuity en severe refractive errors.
As the name suggests, night blindness is one of the symptoms, photophobia is
another. The variation in clinical symptoms (visual acuity, refractive error,
night blindness, photophobia, colour vision, nystagmus, strabismus, ERG
amplitude, threshold of dark adaptation) varies between CSNB1 and CSNB2 but
also between patients with the same mutated gene or even with the same
mutation. Because little is known about the variable expressions of CSNB, the
diagnosis may be missed.

The purpose of this study is to investigate the genotype of a large group of
CSNB patients for which the phenotype is already known. We hope to increase our
understanding of CSNB in order to improve diagnosis, to offer more realistic
prognoses and to gain more scientific background for revalidation. If in some
CSNB patients no mutations can be found in the known genes, the study will be
extended to find yet undiscovered genes that cause the disorder.

CSNB patients and, if necessary, non affected family members will undergo a
blood test. Therefore, 20 ml of blood will be collected at a local hospital.
The DNA tests will be executed at the Netherlands Institute for Neuroscience.
The clinical symptoms of each patient were investigated during regular
examination at the department of ophthalmology of Bartiméus.

Patients and non affected family members will be asked to undergo a blood test
for which 20 ml of blood will be taken. This can take place at a local GP
laboratory or a nearby hospital. Therefore, the strain and risk are minimal. We
also include children and adolescents in this study because they form a large
group within the total group of CSNB patients. Thanks to the increasing
knowledge and expertise with regard to CSNB, correct diagnoses are made more
often especially in children and adolescents.