title: A novel mutation af Cln3 associated with delayed-classic juvenile ceroid lipofuscinois and autophagic vacuolar myopathy.
abstract: Juvenile neuronal-ceroid-lipofuscinosis (JNCL) is a lysosomal storage disease caused by mutations in CLN3. The most frequent mutation is a 1.02-kb deletion that, when homozygous, causes the classical clinical presentation. Patients harboring mutations different than the major deletion show a marked clinical heterogeneity, including protracted disease course with possible involvement of extraneuronal tissues. Cardiac involvement is relatively rare in JNCL and it is usually due to myocardial storage of ceroid-lipofuscinin. Only recently, histopathological findings of autophagic vacuolar myopathy (AVM) were detected in JNCL patients with severe cardiomyopathy. We describe a 35-year-old male showing a delayed-classic JNCL with visual loss in childhood and neurological manifestations only appearing in adult life. He had an unusual CLN3 genotype with an unreported deletion (p.Ala349_Leu350del) and the known p.His315Glnfs*67 mutation. Autophagic vacuolar myopathy was shown by muscle biopsy. At clinical follow-up, moderately increased CPK levels were detected whereas periodic cardiac assessments have been normal to date. Adult neurologists should be aware of protracted JNCL as cause of progressive neurological decline in adults. The occurrence of autophagic vacuolar myopathy necessitates periodic cardiac surveillance, which is not usually an issue in classic JNCL due to early neurological death.
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche of Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. Electronic address: laura.licchetta2@unibo.it.
authors.forename: L
authors.initials: L
authors.lastname: Licchetta
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche of Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bisulli
authors.affiliation: Department of Biochemical Genetics, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Fietz
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche of Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Valentino
authors.affiliation: Neuropathology & Neurology V - IRCCS Foundation "Istituto Neurologico Carlo Besta", Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Morbin
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche of Bologna, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Mostacci
authors.affiliation: Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.
authors.forename: K L
authors.initials: KL
authors.lastname: Oliver
authors.affiliation: Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche of Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Tinuper
mesh_terms: D000328:Adult; D017353:Gene Deletion; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics*; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome
chemical_list: C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones
keywords: Autophagic vacuolar myopathy; CLN3; Delayed-classic JNCL; Juvenile neuronal ceroid lipofuscinosis (JNCL)