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 neur odegenerative disorder caused by the deficiency of lysosomal tripeptidyl pe ptidase I (TPP-I) encoded by the CLN2 gene. We report the first case of ear ly prenatal diagnosis of LINCL by combined enzyme and mutation analysis. TP P-I activity in chorionic villi (CV) was less than 2% of the mean normal co ntrol level and g.1946A > G and 9.3670C > T mutations were demonstrated, as in the two previously affected children. After termination of pregnancy, T PP-I deficiency was confirmed in cultured CV cells and in the fetal skin fi broblasts. The expression of unequivocal TPP-I deficiency in CV demonstrate s that enzyme assay is a reliable option for prenatal diagnosis of LINCL. C opyright (C) 2001 John Wiley & Sons, Ltd.