Autosomal dominant stationary night‐blindness A large family rediscovered

Abstract

In 1909, 2 years after the famous publication by Nettleship, a large family with congenital stationary night-blindness of the 'Nougaret type' was published by the Danish district surgeon, Sigurd Rambusch. In 1990 the 'Rambusch family', still resident in the original area, was sought out and rediscovered, at which time the reconstructed part of the pedigree comprised more than 200 affected persons in 11 generations. Dark adaptometry and electroretinography were performed on a few affected family members, including a descendant with a uniocular affection. The pedigree is presented and recordings of dark adaptation courses and electroretinographical responses from a few family members are demonstrated.

Transgenic mice carrying theH258N mutation in the gene encoding the β-subunit of phosphodiesterase-6 (PDE6B) provide a model for human congenital stationary night blindness

“…The deviation of bright flash ERGs in the six index CSNB patients in the Rambusch family reflected different degrees of disease expression, and varying degrees of electronegativity [Rosenberg et al, 1991]. Thus, the fact that expression of CSNB is heterogeneous in Rambusch family members [Rosenberg et al, 1991] with the same H258N mutation, indicates that factors other than the PDE6B gene itself contribute to the pathophysiology of this retinal dystrophy. Immunoblot analysis of PDE6 subunit expression in control and H258N ROSs.…”

“…They were also similar to humans with the most common form of CSNB (X-linked), that usually demonstrate a marked selective loss of the b-wave with relatively normal a-waves (i.e., an electronegative type of ERG); the defect in X-linked CSNB has been suggested to lie downstream to the photoreceptor neurons, possibly in the ON-bipolar cells or their interconnections [Hood and Birch, 1996]. The sensitivity of ON-bipolar cells may be limited by their increased PDE6 dark activity and the consequent photoreceptor noise, thereby diminishing the optimal interpretation of signalto-noise and, ultimately, visual sensitivity-as seen in some Rambusch family members [Rosenberg et al, 1991].…”

“…Affected individuals achieved 20/20 vision, but had dark adaptation thresholds elevated by 2.5 to 3.0 logarithmic units [Rosenberg et al, 1991], Under dark-adapted conditions, some affected individuals in the Rambusch family demonstrated reduced b-wave amplitudes but relatively normal a-waves [Rosenberg et al, 1991]; this study concluded that "the b-wave exhibited pronounced reduction in amplitude" [Rosenberg et al, 1991], The light-adapted cone 32-Hz white flickering responses obtained from these individuals were described as having "normal or slightly reduced amplitudes and normal implicit times"; the maximal dark-adapted electroretinogram (ERG) responses were mildly electronegative (i.e., a reduced b-to a-wave amplitude ratio) with a normal a-wave confirming normal photoreceptor function, but a reduced b-wave in the maximal response.…”

“…A base change in exon 4 that causes a neutral, hydrophilic asparagine (N) to be encoded in place of a basic, hydrophilic histidine (H) in PDE6B was found to be associated with CSNB in the Sorensen family, first described by Rambusch in 1909 [Gal et al, 1994;Rosenberg et al, 1991]. The Rambusch pedigree consisted of 200 affected individuals over 11 generations.…”

Electroretinogram in Hereditary Retinal Disorders

“…The cone responses were only slightly impaired (Lam, 2005). One another autosomal dominant CSNB pedigree was reported by Rambusch in 1909 in a Danish family (Rosenberg et al, 1991). ERG responses in the Rambusch pedigree are similar to those of Nougaret CSNB and resemble the ERG responses of the Riggs CSNB type (Lam, 2005).…”