A clinical and electrophysiological case study of a child with a novel frame shift mutation in the CACNA1F and missense variation of RIMS1 genes.
CACNA1F
CSNB2
Crossed asymmetry
Electroretinogram
Flash visual evoked potential
Incomplete congenital stationary night blindness
Nystagmus
RIMS1 electronegative
Retina
Journal
Documenta ophthalmologica. Advances in ophthalmology
ISSN: 1573-2622
Titre abrégé: Doc Ophthalmol
Pays: Netherlands
ID NLM: 0370667
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
16
01
2022
accepted:
07
07
2022
pubmed:
11
8
2022
medline:
16
9
2022
entrez:
10
8
2022
Statut:
ppublish
Résumé
The purpose of this paper is to present a case study illustrating the importance of electrophysiological investigation in the diagnosis and serial monitoring of isolated congenital nystagmus. Serial electophysiological monitoring was undertaken in the male proband over a 9-year period commencing with initial assessment at 12 weeks of age: Skin electroretinograms (sERGs) were initially absent but subsequently revealed low-amplitude responses, electronegative morphologies and notched flicker responses suggestive of incomplete congenital stationary night blindness (CSNB2), but with an absent dark-adapted rod-specific response, while flash visual evoked potentials (fVEPs) demonstrated persistent crossed asymmetry, typical of albinoid misrouting of the optic nerves. Molecular investigation confirmed a novel hemizygous frame shift mutation in the CACNA1F gene, considered to be pathogenic and causative of X-linked CSNB2; additionally, a novel heterozygous missense variation in one copy of the RIMS1 gene was identified, pathogenic mutations of which underpin late-onset autosomal dominant cone-rod dystrophy (type 7). Segregation studies confirmed maternal inheritance of both mutations in the clinically asymptomatic mother in whom depressed rod-specific responses were confirmed on sERG. The child's visual acuity has remained stable as have the sERGs which have been verified by recordings using scleral electrodes. The importance of recording ERGs as part of evaluating infants who present with nystagmus, even with a normal fundus appearance, is supported. Further, sERGs were able to distinguish an apparent variant of CSNB2 and could give consistent results over many years. FVEP results add to the evidence that albinoid misrouting of the optic nerves may occur in cases of CSNB2. ERGs and fVEPs can provide valuable information in discriminating the relative diagnostic importance of multiple genetic abnormalities.
Identifiants
pubmed: 35947237
doi: 10.1007/s10633-022-09892-w
pii: 10.1007/s10633-022-09892-w
doi:
Substances chimiques
CACNA1F protein, human
0
Calcium Channels, L-Type
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
163-174Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2022. Crown.
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