Electrophysiological findings of neuronal ceroid lipofuscinosis in heterozygotes

Abstract

Nineteen obligate heterozygotes, 8 individuals at risk of being heterozygote, and 10 patients afflicted with four different forms of neuronal ceroid lipofuscinosis were examined electrophysiologically. The group of obligate heterozygotes was compared to age-matched control groups. Statistically significant differences were found between scotopic b-wave amplitudes, P-ERG amplitudes, and EOG light peaks of the obligate carriers of the juvenile type and the control subjects. The photopic L-ERGs and the latencies of the VEPs were mostly within the normal range. The findings represent the first evidence of functional ophthalmological changes in obligate carriers of neuronal ceroid lipofuscinosis and demonstrate that heterozygotes with certain hereditary autosomal recessive diseases may manifest subtle functional signs.

Ultrastructure of the Retina in Adult Neuronal Ceroid Lipofuscinosis

“…In this context, it is of interest to mention that another patient with adult NCL from a family with three brothers affected had an electroretinographic decrease of the b-wave in the scotopic electroretinogram with normal photopic ERG [Vercruyssen et al, 1982] whose retinal layer was found preserved by light microscopy and contained granulocurvilinear lipopigments in ganglion cells [Martin et al, 1987]. This observation is similar to that recorded reduction in scotopic b-wave amplitudes in obligate heterozygotes without visual impairment in juvenile NCL [Gottlob et al, 1988]. They may further be interpreted as (2) representing two separate disorders, adult NCL and unrelated retinitis pigmentosa, and (3) representing protracted juvenile NCL in which the retina appeared to be regularly involved [Goebel et al, 1976].…”

Neurodevelopmental delay in the Cln3Δex7/8 mouse model for Batten disease

“…Nevertheless, at this point, we cannot fully discard a possible influence of alternative Cln3 transcripts on the observed phenotype, and further studies at the biochemical and molecular levels are necessary to increase our understanding on this aspect. Irrespective of the underlying mechanism, it is interesting to note that existing studies in human patients have documented brain structural abnormalities and functional ophthalmological changes in JNCL carriers (Gottlob et al 1988; Sayit et al 2002), suggesting that heterozygous human carriers may also exhibit mild neurological alterations.…”

“…As symptoms in JNCL emerge in childhood and several studies point to early initiation of JNCL disease process (Cotman et al 2002; Herrmann et al 2008; Kovacs et al 2006; Lake 1993), special attention should be placed in characterizing behavioural alterations at early ages. In addition, the heterozygous Cln3 Δex7/ 8 knock‐in mice should also be characterized because mild alterations have also been reported in JNCL carriers (Gottlob et al 1988; Sayit et al 2002). Therefore, in the present study, we have applied behavioural paradigms suitable to study sensorial and motor capabilities in developing wild type, heterozygous and homozygous Cln3 Δex7/ 8 knock‐in preweaning pups.…”

Mutation del 1,02kb in the CLN3 gene and extrapyramidal syndrome

“…Также не-обходимо отметить, что данные очаги являются крайне неспецифичными -их наличие может быть обусловлено демиелинизацией или глиозом, не связанными с носи-тельством мутаций в гене CLN3. Тем не менее в литерату-ре имеются данные о легких нарушениях и субклиниче-ском поражении сетчатки у близких родственников паци-ентов с ювенильным НЦЛ [16], однако последние иссле-дования опровергают развитие ретинальных нарушений у CLN3-гетерозигот [17].…”