title: The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.
abstract: The neuronal ceroid lipofuscinoses (NCLs) are the commonest neurodegenerative disorders of children. The aims of this study were to determine the incidence of NCL in Newfoundland, identify the causative genes, and analyze the relationship between phenotype and genotype. Patients with NCL diagnosed between 1960 and 2005 were ascertained through the provincial genetics and pediatric neurology clinics. Fifty-two patients from 34 families were identified. DNA was obtained from 28/34 (82%) families; 18 families had mutations in the CLN2 gene, comprising five different mutations of which two were novel. One family had a CLN3 mutation, another had a novel mutation in CLN5, and five families shared the same mutation in CLN6. One family was misdiagnosed, and in two, molecular testing was inconclusive. Disease from CLN2 mutations had an earlier presentation (p = 0.003) and seizure onset (p < 0.001) compared with CLN6 mutation. There was a slower clinical course for those with CLN5 mutation compared with CLN2 mutation. NCL in Newfoundland has a high incidence, 1 in 7353 live births, and shows extensive genetic heterogeneity. The incidence of late infantile NCL, 9.0 per 100,000 (or 1 in 11,161) live births, is the highest reported in the world.
authors.affiliation: Department of Pediatrics, Memorial University of Newfoundland, St John's, Newfoundland, Canada. smoore@mun.ca
authors.forename: S J
authors.initials: SJ
authors.lastname: Moore
authors.forename: D J
authors.initials: DJ
authors.lastname: Buckley
authors.forename: A
authors.initials: A
authors.lastname: MacMillan
authors.forename: H D
authors.initials: HD
authors.lastname: Marshall
authors.forename: L
authors.initials: L
authors.lastname: Steele
authors.forename: P N
authors.initials: PN
authors.lastname: Ray
authors.forename: Z
authors.initials: Z
authors.lastname: Nawaz
authors.forename: B
authors.initials: B
authors.lastname: Baskin
authors.forename: M
authors.initials: M
authors.lastname: Frecker
authors.forename: S M
authors.initials: SM
authors.lastname: Carr
authors.forename: E
authors.initials: E
authors.lastname: Ives
authors.forename: P S
authors.initials: PS
authors.lastname: Parfrey
mesh_terms: D000293:Adolescent; D000626:Aminopeptidases; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases / Q000235:genetics; D005190:Family; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D009523:Newfoundland and Labrador / Q000453:epidemiology; D010641:Phenotype; D057057:Serine Proteases; D000091346:Tripeptidyl-Peptidase 1
chemical_list: C113332:CLN5 protein, human; C447500:CLN6 protein, human; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D000091346:Tripeptidyl-Peptidase 1; D010450:Endopeptidases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human