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.
- Prenatal Diagnosis 10/2000; 20(10):819-21. DOI:10.1002/1097-0223(200010)20:10<819::AID-PD933>3.0.CO;2-M · 3.27 Impact Factor
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ABSTRACT: The recent development of simple, fluorogenic enzyme assays for infantile and late infantile neuronal ceroid lipofuscinosis (INCL and LINCL; CLN1 and CLN2) has greatly facilitated the diagnostic process for these diseases. In leucocytes and fibroblasts from INCL (n = 38) patients we found profound deficiencies of palmitoyl-protein thioesterase I (PPT1), the residual activity was < 5% of mean control activity. In fibroblasts from LINCL patients we found a similar deficiency of tripeptidyl-peptidase I activity (TPP-I), with < 2% activity in 16 patients. The residual TPP-I activity in leucocytes from LINCL patients seemed substantially higher. We also showed the feasibility of reliable prenatal enzyme analysis. In five first-trimester and two second-trimester prenatal analyses for INCL, four affected foetuses were detected (PPT activity 3-6%). Two first trimester pregnancies at risk for LINCL were analysed and a clear TPP-I deficiency was detected in both cases (TPP-I activity 3-4%). The first patient with adult neuronal ceroid lipofuscinosis (ANCL) due to a deficiency of PPT is presented; her present age is 53 years and the onset of the disease was at 38 years with psychiatric symptoms.European Journal of Paediatric Neurology 01/2001; 5 Suppl A:189-92. DOI:10.1053/ejpn.2001.0509 · 2.30 Impact Factor
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ABSTRACT: Congenital ataxias are a heterogeneous group of predominantly nonprogressive disorders characterized by hypotonia, developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We performed a genome-wide screen on a large inbred Lebanese family presenting a nonprogressive autosomal recessive congenital cerebellar ataxia associated with short stature (MIM 213200), already described by Mégarbané and colleagues. The disease locus was assigned to a 12.1 cM interval on chromosome 9q34-9qter between D9S67 and D9S312. Differential diagnosis with other hereditary ataxias linked to the same region is discussed.Annals of Neurology 08/2001; 50(2):250-3. DOI:10.1002/ana.1286 · 9.98 Impact Factor
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