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. Copyright © 2001 John Wiley & Sons, Ltd.