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30.03.2021 | Original article

A novel deletion variant in CLN3 with highly variable expressivity is responsible for juvenile neuronal ceroid lipofuscinoses

verfasst von: Naser Gilani, Ehsan Razmara, Mehmet Ozaslan, Ihsan Kareem Abdulzahra, Saeid Arzhang, Ali Reza Tavasoli, Masoud Garshasbi

Erschienen in: Acta Neurologica Belgica | Ausgabe 3/2021

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Abstract

Mutations in CLN3 (OMIM: 607042) are associated with juvenile neuronal ceroid lipofuscinoses (JNCL)—a rare neurodegenerative disease with early retinal degeneration and progressive neurologic deterioration. The study aimed to determine the underlying genetic factors justifying the NCL phenotype in a large Iraqi consanguineous family. Four affected individuals with an initial diagnosis of NCL were recruited. By doing neuroimaging and also pertinent clinical examinations, e.g. fundus examination, due to heterogeneity of neurodevelopmental disorders, the proband was subjected to the paired-end whole-exome sequencing to identify underlying genetic factors. The candidate variant was also confirmed by Sanger sequencing. Various in silico predictions were used to show the pathogenicity of the variant. This study revealed a novel homozygous frameshift variant—NM_000086.2: c.1127del; p.(Leu376Argfs*15)—in the exon 14 of the CLN3 gene as the most likely disease-causing variant. Three out of 4 patients showed bilateral vision loss (< 7 years) and retinal degeneration with macular changes in both eyes. Electroencephalography demonstrated the loss of normal posterior alpha rhythm and also low amplitude multifocal slow waves. Brain magnetic resonance imaging of the patients with a high degree of deterioration showed mild cerebral and cerebellar cortical atrophy, mild ventriculomegaly, thinning of the corpus callosum and vermis, and non-specific periventricular white matter signal changes in the occipital area. The novel biallelic deletion variant of CLN3 was identified that most probably led to JNCL with variable expressivity of the phenotype. This study also expanded our understanding of the clinical and genetic spectrum of JNCL.

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Titel: A novel deletion variant in CLN3 with highly variable expressivity is responsible for juvenile neuronal ceroid lipofuscinoses
verfasst von: Naser Gilani
Ehsan Razmara
Mehmet Ozaslan
Ihsan Kareem Abdulzahra
Saeid Arzhang
Ali Reza Tavasoli
Masoud Garshasbi
Publikationsdatum: 30.03.2021
Verlag: Springer International Publishing
Erschienen in: Acta Neurologica Belgica / Ausgabe 3/2021
Print ISSN: 0300-9009
Elektronische ISSN: 2240-2993
DOI: https://doi.org/10.1007/s13760-021-01655-9

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