An integrated strategy for the diagnosis of neuronal ceroid lipofuscinosis types 1 (CLN1) and 2 (CLN2) in eleven Latin American patients.
The neuronal ceroid lipofuscinoses (NCLs) are a family of progressive neurodegenerative diseases that are characterized by the cellular accumulation of ceroid lipofuscin-like bodies. NCL type 1 (CLN1) and type 2 (CLN2) are caused by deficiencies of the lysosomal enzymes palmitoyl-protein thioesterase 1 (PPT-1) and tripeptidyl peptidase 1 (TPP-1), respectively. In this study, 118 Latin American patients were examined for NCL using an integrated multidisciplinary program. This revealed two patients affected by CLN1 and nine by CLN2. Both CLN1 patients had a juvenile-onset phenotype with mutation studies of one patient demonstrating the known mutation p.Arg151X and a novel mutation in intron 3, c.363-3T>G. Six of the CLN2 patients presented with the 'classical' late-infantile phenotype. The remaining three patients, who were siblings, presented with a 'protracted' phenotype and had a higher level of residual TPP-1 activity than the 'classical' CLN2 patients. Genotype analysis of the TPP1 gene in the 'classical' CLN2 patients showed the presence of the known mutation p.Arg208X and the novel mutations p.Leu104X, p.Asp276Val, and p.Ala453Val. The siblings with the 'protracted' phenotype were heterozygous for two known TPP1 mutations, p.Gln66X and c.887-10A>G. This multidisciplinary program is also being used to diagnose other NCL types.
Centre for the Study of Inherited Metabolic Diseases (CEMECO), Children's Hospital, School of Medicine, National University Cordoba, Cordoba, Argentina.
R
R
Kohan
I A
IA
Cismondi
R Dodelson
RD
Kremer
V J
VJ
Muller
N
N
Guelbert
V Tapia
VT
Anzolini
M J
MJ
Fietz
A M Oller
AM
Ramírez
I Noher
IN
Halac
D000626:Aminopeptidases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D001118:Argentina; D002648:Child; D002675:Child, Preschool; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D057057:Serine Proteases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013869:Thiolester Hydrolases; D000091346:Tripeptidyl-Peptidase 1
D008565:Membrane Proteins; D000091346:Tripeptidyl-Peptidase 1; D013869:Thiolester Hydrolases; C416054:PPT1 protein, human; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human