title: Novel CLN1 mutation in two Italian sibs with late infantile neuronal ceroid lipofuscinosis.
abstract: We detected a novel CLN1 mutation (c.125-15t>g) in two Italian siblings. The clinical phenotype is that of a variant late-infantile neuronal ceroid lipofuscinosis and consisted of early-onset visual loss, psychomotor deterioration, and seizures. Ultrastructurally, granular osmiophilic deposits were found in skin biopsy of both patients. The novel mutation occurs in the acceptor sequences for splicing and leads to skipping of multiple exons. This predicts a protein lacking part or all of the active site of the enzyme and the palmitate-binding pocket. Consequently, biochemical activity of the palmitoyl protein thioesterase-1 enzyme was drastically reduced. The new mutation was not identified in a large set of ethnically matched control chromosomes. Our findings support the notion that CLN1 patients are not rare in Southern Europe and facilitate DNA-based mutation and carrier testing in this family.
authors.affiliation: Division of Infantile, Neuropsychiatry, Department of Medical and Surgical Pediatrics, University of Messina, via Consolare Valeria 98125 Messina, Italy. mbonsignore@unime.it
authors.forename: Maria
authors.initials: M
authors.lastname: Bonsignore
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Gabriella
authors.initials: G
authors.lastname: Di Rosa
authors.forename: Fiorella
authors.initials: F
authors.lastname: Piemonte
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: Alessandro
authors.initials: A
authors.lastname: Simonati
authors.forename: Filippo
authors.initials: F
authors.lastname: Calamoneri
authors.forename: Gaetano
authors.initials: G
authors.lastname: Tortorella
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000502:physiology*; D009468:Neuromuscular Diseases / Q000209:etiology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology; D010170:Palmitoyl-CoA Hydrolase / Q000172:deficiency / Q000235:genetics; D010641:Phenotype; D012640:Seizures / Q000209:etiology; D012867:Skin / Q000473:pathology; D013869:Thiolester Hydrolases; D014786:Vision Disorders / Q000209:etiology
chemical_list: D008565:Membrane Proteins; D013869:Thiolester Hydrolases; D010170:Palmitoyl-CoA Hydrolase; C416054:PPT1 protein, human