Pedigrees of family A and family B with autosomal recessive achromatopsia originating from the United Arab Emirates and carrying mutations in the CNGA3 gene

Family A has two branches carrying either the two heterozygous mutations R283W and G397V or being homozygous for the mutation G397V due to consanguinity of the parents. Patients of family B are both homozygous for the mutation R283W in the CNGA3 gene. Squares indicate males and circles females. Open symbols indicate healthy individuals, while shadings designate the affected patients. Arrows point to family members for whom DNA samples were available for genetic analysis. CNGA3 genotypes are given below each analyzed individual.<p><b>Copyright information:</b></p><p>Taken from " mutations in two United Arab Emirates families with achromatopsia"</p><p></p><p>Molecular Vision 2008;14():1293-1297.</p><p>Published online 10 Jul 2008</p><p>PMCID:PMC2464613.</p><p></p

ISCEV standard Ganzfeld ERG responses of a representative patient of each group compared to a normal subject.

<p>Patient BD27.I in the upper panels represents the NOP group, while the result of patient BCM5 in the middle panels is an example for the ALP group. The normal subject is represented in the bottom panels. The patients' findings show the characteristic features of the scotopic ERG (dark-adapted (DA)) and the small photopic responses (light adapted (LA). Notice the missing oscillatory potentials on the rising b-wave in patients. (Color coding in each panel: red curves show results of the right eye (OD), blue curves show results of the left eye (OS)).</p

Scotopic flicker series.

<p>Magnitude (A) and phase (B) of scotopic flicker responses to stimuli of increasing flicker frequency are presented. Significance levels are color-coded in each figure, the 95% confidence band of normal subjects are marked with grey. The amplitudes of the patients are below normal and not significant for stimuli faster than 15 Hz. The phase shift, however, seems to be independent from flicker frequency.</p

Photopic negative response (PhNR).

<p>Photopic single flash response waveforms illustrating the photopic negative response (PhNR) at increasing stimulus intensities (from top to the bottom in each panel) are shown in a normal subject (on the left) and the waveforms of two representative patients of the ALP (patient BCM5 in the middle) and NOP group (patient RCD307 on the right). Notice, that patients lack the PhNR in the given intensity range.</p

Intensity-response function kinetics under scotopic conditions.

<p>The single flash response a- and b-wave amplitudes (A) and implicit times (B) to increasing stimulus intensities are presented for both groups (upper subjects: NOP group, lower subjects: ALP group; the 95% confidence band of normal subjects is marked with grey). While the a-wave amplitude slowly and continuously increases, the b-wave amplitude stays low until the flash intensity reaches −2.5 log cd*s/m². While peak implicit times of the a-wave responses are prolonged for all flash intensities, the implicit times of the b-wave approaches the normal range with increasing flash intensity.</p

Analysis of the scotopic a-wave (<i>P_III</i> response).

<p>(A) Scotopic response a-waves to increasing flash intensities show continuous increasing response amplitudes in the normal subject (full lines). The patient's responses (chain lines) also show continuous increasing amplitudes up to a flash intensity of 4.2 log td*s (green color coding), but a lower response amplitude to the flash with highest intensity (red color coding). Therefore responses to highest flash intensity were excluded from a-wave analysis. Interestingly, while R² of the fits in normal subjects was above 0.02 in 2 eyes only, it was higher in 7 of the patient eyes (B). The difference in goodness of the fit is seen in the normal subject (C) and in the representative patient BCM5 (D).</p

Dark adaptation curves of the patients of both groups compared to normal subjects.

<p>The left panel shows the cone (red stimuli), the right panel the rod function (green stimuli) of the NOP and ALP groups (the 95% confidence band of normal subjects is marked with grey). The threshold elevation for both target colors is biggest for two patients of the NOP group.</p

Morphological findings.

<p>Fundus photographs of the right eye, FAF and spectral domain OCT images of both eyes of six patients illustrating the variability and extent of foveal changes (NOP group: upper three patients, ALP group: lower three patients). Notice the age-related changes, epiretinal gliosis and macular hole formation on the left eye of the RCD307 patient.</p

Intensity-response function kinetics under photopic conditions.

<p>Photopic response b-wave amplitudes are shown in (A) and implicit times in (B), the 95% confidence band of normal subjects is marked with grey. The photopic hill phenomenon can be observed in normals, however, this phenomenon seems to be missing in patients. Implicit times in both patient groups are moderately delayed (upper subjects: NOP group, lower subjects: ALP group).</p

Structure of the Kv8.2 potassium channel and mutation sites detected in our patients.

<p>The mutation pairs in each box represent the genetic findings of each patient. The genetic findings of the two sibling pairs are shown once, since the siblings share the same mutation constellation.</p