First-trimester diagnosis of late-infantile neuronal ceroid lipofuscinosis (LINCL) by tripeptidyl peptidase I assay and CLN2 mutation analysis.
Late-infantile neuronal ceroid lipofuscinosis (LINCL) is a progressive neurodegenerative disorder caused by the deficiency of lysosomal tripeptidyl peptidase I (TPP-I) encoded by the CLN2 gene. We report the first case of early prenatal diagnosis of LINCL by combined enzyme and mutation analysis. TPP-I activity in chorionic villi (CV) was less than 2% of the mean normal control level and g.1946A > G and g.3670C > T mutations were demonstrated, as in the two previously affected children. After termination of pregnancy, TPP-I deficiency was confirmed in cultured CV cells and in the fetal skin fibroblasts. The expression of unequivocal TPP-I deficiency in CV demonstrates that enzyme assay is a reliable option for prenatal diagnosis of LINCL.
Department of Clinical Genetics, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands. kleijer@kgen.fgg.eur.nl
W J
WJ
Kleijer
O P
OP
van Diggelen
J L
JL
Keulemans
M
M
Losekoot
V H
VH
Garritsen
H
H
Stroink
D
D
Majoor-Krakauer
P F
PF
Franken
M C
MC
Eurlings
P E
PE
Taschner
F J
FJ
Los
R J
RJ
Galjaard
D000626:Aminopeptidases; D002824:Chorionic Villi / Q000201:enzymology; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D006801:Humans; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis; D000091346:Tripeptidyl-Peptidase 1
D000091346:Tripeptidyl-Peptidase 1; D010450:Endopeptidases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human