Retinal Function in Carriers of Bardet-Biedl Syndrome

Abstract

To test the hypothesis that carriers of Bardet-Biedl syndrome have abnormal rod-mediated responses. Methods: Parents (n = 26) of children with Bardet-Biedl syndrome (BBS), who are obligate carriers of BBS, consented to scotopic, full-field electroretinography (ERG). Responses were recorded over a 4 to 5 log unit range, up to a maximum stimulus of approximately +3.6 log scotopic troland seconds. The parameters of activation of the rod photoresponse, S (sensitivity parameter) and R mp3 (amplitude of the saturated rod response), were derived by fitting a transduction model to the ERG awaves. For the b-wave, the stimulus producing a half maximum response (log) and the saturated amplitude (V max) were determined. The model of the rod photoresponse was subtracted from the intact ERG to demonstrate a corneal positive potential (P 2) , and log k P2 and P 2max were determined. The carriers' ERG responses were compared with those of healthy control subjects (n=26). Main Outcome Measures: Sensitivity (S, log , and log k P2) and saturated amplitude (R mp3 , V max , and P 2max) of receptoral and postreceptoral response components. Results: All parents had decreased P 2 sensitivity, and most (15 [60%] of 26) had decreased b-wave sensitivity. The rod photoresponse sensitivity and the saturated amplitudes of the rod cell response, b-wave and P 2 , did not differ significantly between carriers and controls. Conclusions: Diminished P 2 sensitivity is characteristic of the carriers of BBS. The site of the primary defect in the BBS rod pathway appears to be proximal to the outer segments, most likely before the rod-bipolar cell synapse.

PIII and Derived PII Analysis in a Patient with Retinal Dysfunction with Supernormal Scotopic ERG

“…This analysis was already used in this disorder [8], and our results were the same as those in that report; greatly slower and larger than the responses for the normal subject. This characteristic of the derived PII response in 'supernormal and delayed rod ERG syndrome' is very unique among disorders whose derived PII responses were analyzed [20,21]. When our patient and the patients by Hood et al [8] are compared, it is quite interesting that the PIII components were completely different, yet the mean delays of the derived PII components were almost equivalent (our patient, about 15 msec; Hood et al, about 16 msec [8]).…”

Phenotypic variability of Bardet-Biedl syndrome: focusing on the kidney

“…According to different reports, they should be at risk of developing obesity, hypertension, retinal dysfunction, and renal cancers and abnormalities [72][73][74][75]. However, this risk was not confirmed by two large studies comparing BBS relatives with or without a heterozygous mutation [76,77].…”

Bardet-Biedl Syndrome

“…The dominant-negative model may explain the increased incidence of heterozygous BBS gene mutation carriers in patients with BBS syndrome as well as the role of single-copy gene alterations in triallelic inheritance [Fauser et al, 2003;Hichri et al, 2005;Hjortshøj et al, 2010]. Some reports indicate an increased incidence of isolated BBS-related symptoms in parents of BBS patients and/or heterozygous carriers of the BBS gene mutations, while other studies disagree with this statement [Croft et al, 1995;Beales et al, 1999;Cox et al, 2003;Hjortshøj et al, 2007;Kim et al, 2007;Webb et al, 2009].…”