title: Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6.
abstract: The neuronal ceroid lipofuscinoses (NCL) are heterogeneous neurodegenerative disorders with typical autofluorescence material stored in tissues. Ten clinical NCL forms and eight causative genes are known. Mutations in CLN6 have been reported in roughly 30 patients, mostly in association with the variant late-infantile NCL (v-LINCL) phenotype. We screened CLN6 in 30 children from a cohort of 53 v-LINCL cases and revised their clinical and ultrastructural features. We detected 11 mutations, eight of which are novel, all predicting a direct impairing of the putative gene function. No clear-cut genotype-phenotype correlations were observed, with inter- and intra-familial variability evident for few recurrent mutations. Ultrastructural findings were suggestive of an impaired regulation of the autophagic vacuoles turnover. While expanding the array of CLN6 mutations, we showed that more than half of our v-LINCL cases lack a DNA confirmation and further molecular etiologies are to be searched.
authors.affiliation: Molecular Medicine, Neurology, and Pathology, IRCCS-Bambino Gesù Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Cannelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Simonati
authors.forename: Chiara
authors.initials: C
authors.lastname: Aiello
authors.forename: Chiara
authors.initials: C
authors.lastname: Barzaghi
authors.forename: Francesco
authors.initials: F
authors.lastname: Pezzini
authors.forename: Maria Roberta
authors.initials: MR
authors.lastname: Cilio
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Michela
authors.initials: M
authors.lastname: Morbin
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dalla Bernardina
authors.forename: Tiziana
authors.initials: T
authors.lastname: Granata
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Federica
authors.initials: F
authors.lastname: Invernizzi
authors.forename: Alice
authors.initials: A
authors.lastname: Pessagno
authors.forename: Renata
authors.initials: R
authors.lastname: Boldrini
authors.forename: Federica
authors.initials: F
authors.lastname: Zibordi
authors.forename: Luisa
authors.initials: L
authors.lastname: Grazian
authors.forename: Dianela
authors.initials: D
authors.lastname: Claps
authors.forename: Rosalba
authors.initials: R
authors.lastname: Carrozzo
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mole
authors.forename: Nardo
authors.initials: N
authors.lastname: Nardocci
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000293:Adolescent; D001343:Autophagy / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000648:ultrastructure*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: C447500:CLN6 protein, human; D008565:Membrane Proteins