Novel CLN1 mutation in two Italian sibs with late infantile neuronal ceroid lipofuscinosis.
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.
Bonsignore
Maria
M
Division of Infantile, Neuropsychiatry, Department of Medical and Surgical Pediatrics, University of Messina, via Consolare Valeria 98125 Messina, Italy. mbonsignore@unime.it
Tessa
Alessandra
A
Di Rosa
Gabriella
G
Piemonte
Fiorella
F
Dionisi-Vici
Carlo
C
Simonati
Alessandro
A
Calamoneri
Filippo
F
Tortorella
Gaetano
G
Santorelli
Filippo M
FM
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
D008565:Membrane Proteins; D013869:Thiolester Hydrolases; D010170:Palmitoyl-CoA Hydrolase; C416054:PPT1 protein, human