First-trimester diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) using PPT enzyme assay and CLN1 mutation analysis.
ABSTRACT 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.
- [Show abstract] [Hide abstract]
ABSTRACT: We herein report on a Japanese boy with infantile neuronal ceroid lipofuscinosis (INCL). He was born of incest to a girl and her maternal uncle. His development was normal at 12 months, and began to display regression at 14 months. He lost his social smile and tracking eye movement at 16 months, and could not stand and developed severe hypotonic tetraplegia at 19 months. Myoclonic movement was observed in his trunk, eye and extremities. His height, body weight and head circumstance had been normal. Both MRI and CT scans of his head showed severe cerebral, cerebellar and brainstem atrophy. The electroretinogram showed a decrease in amplitude. Enzyme studies revealed a deficiency of palmitoyl-protein thioesterase activity in his lymphocytes at 0.98 nmol/h/mg protein (control: 90.99+/-34.23). This is the first case of INCL in Japan diagnosed by enzyme activity deficiency.Brain and Development 06/2008; 30(5):370-3. · 1.67 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The Neuronal Ceroid Lipofuscinoses (NCLs) are the most common group of neurodegenerative disorders of childhood. While mutations in eight different genes have been shown to be responsible for these clinically distinct types of NCL, the NCLs share many clinical and pathological similarities. We have conducted an exhaustive Basic Local Alignment Search Tool (BLAST) analysis of the human protein sequences for each of the eight known NCL proteins- CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8 and CLN10. The number of homologous species per CLN-protein identified by BLAST searches varies depending on the parameters set for the BLAST search. For example, a lower threshold is able to pull up more homologous sequences whereas a higher threshold decreases this number. Nevertheless, the clade confines are consistent despite this variation in BLAST searching parameters. Further phylogenetic analyses on the appearance of NCL proteins through evolution reveals a different time line for the appearance of the CLN-proteins. Moreover, divergence of each protein shows a different pattern, providing important clues on the evolving role of these proteins. We present and review in-depth bioinformatic analysis of the NCL proteins and classify the CLN-proteins into families based on their structures and evolutionary relationships, respectively. Based on these analyses, we have grouped the CLN-proteins into common clades indicating a common evolving pathway within the evolutionary tree of life. CLN2 is grouped in Eubacteria, CLN1 and CLN10 in Viridiplantae, CLN3 in Fungi/ Metazoa, CLN7 in Bilateria and CLN5, CLN6 and CLN8 in Euteleostomi.Current Genomics 05/2008; 9(2):115-36. · 2.48 Impact Factor
- Studies in Surface Science and Catalysis - STUD SURF SCI CATAL. 01/2005; 158:2001-2008.