title: An Australasian diagnostic service for the neuronal ceroid lipofuscinoses.
abstract: The neuronal ceroid lipofuscinoses (NCLs) are a family of related genetic disorders that together are believed to affect one child in every 12,500 births in the USA. Our laboratory has developed a diagnostic service for classical late infantile neuronal ceroid lipofuscinosis (LINCL) by assay of tripeptidyl-peptidase I (TPP-I) activity using the fluorogenic peptide substrate Ala-Ala-Phe aminomethylcoumarin, followed by a screen for three mutations in the CLN2 gene. In addition, we have also begun to offer a limited diagnostic service for the juvenile (JNCL) and infantile (INCL) forms of the disease on the basis of mutation analysis of the CLN3 and CLN1 genes, respectively. Retrospective analysis of Australasian patients with a clinical suspicion of NCL has revealed that six are affected by LINCL, six by JNCL and, to date, two by INCL. Mutation analysis of our LINCL patients has shown that the three screened mutations, namely, the nonsense mutation R208X and the splice mutations IVS5-1 G > C and IVS5-1 G > A, constitute 83% of alleles.
authors.affiliation: Women's and Children's Hospital, 72 King William Rd, North Adelaide, Australia.
authors.forename: V J
authors.initials: VJ
authors.lastname: Muller
authors.forename: B C
authors.initials: BC
authors.lastname: Paton
authors.forename: M J
authors.initials: MJ
authors.lastname: Fietz
mesh_terms: D000626:Aminopeptidases; D001315:Australia; D002648:Child; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases / Q000032:analysis / Q000235:genetics; D005820:Genetic Testing / Q000458:organization & administration*; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D010447:Peptide Hydrolases / Q000235:genetics; D016730:Program Development; D011506:Proteins / Q000235:genetics; D012189:Retrospective Studies; D057057:Serine Proteases; D013869:Thiolester Hydrolases; D000091346:Tripeptidyl-Peptidase 1
chemical_list: C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins; D000091346:Tripeptidyl-Peptidase 1; D013869:Thiolester Hydrolases; C416054:PPT1 protein, human; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human