PMID- 19793312 OWN - NLM STAT- MEDLINE DCOM- 20100105 LR - 20211203 IS - 1399-0004 (Electronic) IS - 0009-9163 (Linking) VI - 76 IP - 4 DP - 2009 Oct TI - An integrated strategy for the diagnosis of neuronal ceroid lipofuscinosis types 1 (CLN1) and 2 (CLN2) in eleven Latin American patients. PG - 372-82 LID - 10.1111/j.1399-0004.2009.01214.x [doi] AB - 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. FAU - Kohan, R AU - Kohan R AD - Centre for the Study of Inherited Metabolic Diseases (CEMECO), Children's Hospital, School of Medicine, National University Cordoba, Cordoba, Argentina. FAU - Cismondi, I A AU - Cismondi IA FAU - Kremer, R Dodelson AU - Kremer RD FAU - Muller, V J AU - Muller VJ FAU - Guelbert, N AU - Guelbert N FAU - Anzolini, V Tapia AU - Anzolini VT FAU - Fietz, M J AU - Fietz MJ FAU - Ramirez, A M Oller AU - Ramirez AM FAU - Halac, I Noher AU - Halac IN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Denmark TA - Clin Genet JT - Clinical genetics JID - 0253664 RN - 0 (Membrane Proteins) RN - 0 (Tripeptidyl-Peptidase 1) RN - EC 3.1.2.- (Thiolester Hydrolases) RN - EC 3.1.2.22 (PPT1 protein, human) RN - EC 3.4.- (Serine Proteases) RN - EC 3.4.11.- (Aminopeptidases) RN - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases) RN - EC 3.4.14.9 (TPP1 protein, human) SB - IM MH - Aminopeptidases/deficiency/*genetics/metabolism MH - Argentina MH - Child MH - Child, Preschool MH - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/deficiency/*genetics/metabolism MH - Female MH - Genetic Predisposition to Disease/*genetics MH - Genotype MH - Hispanic or Latino MH - Humans MH - Male MH - Membrane Proteins/deficiency/*genetics/metabolism MH - Mutation/genetics MH - Neuronal Ceroid-Lipofuscinoses/*genetics/pathology MH - *Phenotype MH - Serine Proteases/deficiency/*genetics/metabolism MH - Thiolester Hydrolases MH - Tripeptidyl-Peptidase 1 EDAT- 2009/10/02 06:00 MHDA- 2010/01/06 06:00 CRDT- 2009/10/02 06:00 PHST- 2009/10/02 06:00 [entrez] PHST- 2009/10/02 06:00 [pubmed] PHST- 2010/01/06 06:00 [medline] AID - CGE1214 [pii] AID - 10.1111/j.1399-0004.2009.01214.x [doi] PST - ppublish SO - Clin Genet. 2009 Oct;76(4):372-82. doi: 10.1111/j.1399-0004.2009.01214.x.