First-trimester diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) using PPT enzyme assay andCLN1 mutation analysis
Department of Clinical Genetics, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.Prenatal Diagnosis (Impact Factor: 3.27). 07/1999; 19(6):559-62. DOI: 10.1002/(SICI)1097-0223(199906)19:6<559::AID-PD587>3.0.CO;2-8
Infantile neuronal ceroid lipofuscinosis (INCL) is a progressive neurodegenerative disorder in childhood which is caused by the deficiency of the lysosomal palmitoyl-protein thioesterase (PPT) encoded by the CLN1 gene. In a pregnancy at risk for INCL, chorionic villi (CV) were studied using a novel fluorometric PPT enzyme assay in combination with mutation-analysis of the CLN1 gene. The PPT activity in chorionic villi was found to be deficient and homozygosity for the C451T mutation in CLN1 was found. The pregnancy was terminated and the PPT deficiency was confirmed in cultured CV cells as well as in the cultured fetal skin fibroblasts. This report shows the first early prenatal diagnosis of INCL performed by fluorometric enzyme analysis and mutation analysis of the CLN1 gene.
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ABSTRACT: The neuronal ceroid lipofuscinoses (NCLs) collectively constitute the most common group of progressive brain diseases in children. The childhood forms of NCL are recessively inherited monogenic diseases, resulting in progressive dementia and motor problems, epilepsy, blindness and, finally, early death. Pathologically, the NCLs are characterized by accumulation of autofluorescent storage material in the lysosomes of neurons and other cells. The disease is selectively manifested in the central nervous system, so that there is a progressive loss of neurons. This leads to a dramatic cerebral atrophy typical of the early onset forms of NCL. The present review summarizes the knowledge of the biochemistry of NCLs, and discusses the possible pathogenetic mechanisms involved in the neurodegeneration in NCLs.
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