<i>CLN8</i> Mutations Presenting with a Phenotypic Continuum of Neuronal Ceroid Lipofuscinosis—Literature Review and Case Report

• Main Authors: Magdalena Badura-Stronka, Anna Winczewska-Wiktor, Anna Pietrzak, Adam Sebastian Hirschfeld, Tomasz Zemojtel, Katarzyna Wołyńska, Katarzyna Bednarek-Rajewska, Monika Seget-Dubaniewicz, Agnieszka Matheisel, Anna Latos-Bielenska, Barbara Steinborn
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Genes
• Subjects: <i>CLN8</i>; LINCL; lipofuscinosis; mutation; neuronal; ceroid
• Online Access: https://www.mdpi.com/2073-4425/12/7/956

CLN8 is a ubiquitously expressed membrane-spanning protein that localizes primarily in the ER, with partial localization in the ER-Golgi intermediate compartment. Mutations in <i>CLN8</i> cause late-infantile neuronal ceroid lipofuscinosis (LINCL). We describe a female pediatric patient with LINCL. She exhibited a typical phenotype associated with LINCL, except she did not present spontaneous myoclonus, her symptoms occurrence was slower and developed focal sensory visual seizures. In addition, whole-exome sequencing identified a novel homozygous variant in <i>CLN8</i>, c.531G>T, resulting in p.Trp177Cys. Ultrastructural examination featured abundant lipofuscin deposits within mucosal cells, macrophages, and monocytes. We report a novel <i>CLN8</i> mutation as a cause for NCL8 in a girl with developmental delay and epilepsy, cerebellar syndrome, visual loss, and progressive cognitive and motor regression. This case, together with an analysis of the available literature, emphasizes the existence of a continuous spectrum of <i>CLN8</i>-associated phenotypes rather than a sharp distinction between them.