Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6.
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.
Cannelli
Natalia
N
Molecular Medicine, Neurology, and Pathology, IRCCS-Bambino Gesù Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy.
Garavaglia
Barbara
B
Simonati
Alessandro
A
Aiello
Chiara
C
Barzaghi
Chiara
C
Pezzini
Francesco
F
Cilio
Maria Roberta
MR
Biancheri
Roberta
R
Morbin
Michela
M
Dalla Bernardina
Bernardo
B
Granata
Tiziana
T
Tessa
Alessandra
A
Invernizzi
Federica
F
Pessagno
Alice
A
Boldrini
Renata
R
Zibordi
Federica
F
Grazian
Luisa
L
Claps
Dianela
D
Carrozzo
Rosalba
R
Mole
Sara E
SE
Nardocci
Nardo
N
Santorelli
Filippo M
FM
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
C447500:CLN6 protein, human; D008565:Membrane Proteins