PubMed:10191107 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/10191107","sourcedb":"PubMed","sourceid":"10191107","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10191107","text":"Genotype-phenotype correlations in neuronal ceroid lipofuscinosis due to palmitoyl-protein thioesterase deficiency.\nThe infantile form of neuronal ceroid lipofuscinosis (NCL) has been well studied in Finland, where there is a high carrier frequency (1:70) for a single mutation in the causative gene, CLN1, or PPT. We have recently studied a group of 29 NCL subjects in the United States with palmitoyl-protein thioesterase (PPT) deficiency and described 19 different CLN1/PPT mutations in our population. In this report, we present a review of our previous findings, including a more detailed analysis of phenotype-genotype correlations, and present previously unpublished data concerning the clinical manifestations of the disorder in children of families with multiple affected members. Our studies indicate that about half of PPT-deficient patients in the United States are very similar to Finnish infants with INCL, but that a different mutation (R151X) accounts for 40% of U.S. alleles. The Finnish mutation (R122W) is rare in the United States. The other half of U.S. PPT-deficient patients develop symptoms after the age of 2 years, much later than Finnish patients. One common mutation (the \"Scottish\" allele, T75P) accounts for 13% of alleles and results in a juvenile-onset phenotype that is clinically indistinguishable from JNCL with CLN3 mutations. Other rare mutations were also associated with JNCL phenotypes, such as D79G and G250V. A preliminary expression study of two of these mutant enzymes supports the conclusion that juvenile-onset NCL (JNCL with GROD) is caused by missense mutations in the PPT gene that result in mutated enzymes with residual PPT enzyme activity.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1562,"end":1566},"obj":"gene:1201"},{"id":"T1","span":{"begin":1557,"end":1560},"obj":"disease:C0027877"},{"id":"T2","span":{"begin":1617,"end":1620},"obj":"gene:5538"},{"id":"T3","span":{"begin":1557,"end":1560},"obj":"disease:C0027877"},{"id":"T4","span":{"begin":1617,"end":1620},"obj":"gene:5536"},{"id":"T5","span":{"begin":1557,"end":1560},"obj":"disease:C0027877"},{"id":"T6","span":{"begin":1617,"end":1620},"obj":"gene:6863"},{"id":"T7","span":{"begin":1557,"end":1560},"obj":"disease:C0027877"},{"id":"T8","span":{"begin":1671,"end":1674},"obj":"gene:5538"},{"id":"T9","span":{"begin":1557,"end":1560},"obj":"disease:C0027877"},{"id":"T10","span":{"begin":1671,"end":1674},"obj":"gene:5536"},{"id":"T11","span":{"begin":1557,"end":1560},"obj":"disease:C0027877"},{"id":"T12","span":{"begin":1671,"end":1674},"obj":"gene:6863"},{"id":"T13","span":{"begin":1557,"end":1560},"obj":"disease:C0027877"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"},{"id":"R7","pred":"associated_with","subj":"T12","obj":"T13"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"},{"subj":"T8","pred":"source","obj":"DisGeNET"},{"subj":"T9","pred":"source","obj":"DisGeNET"},{"subj":"T10","pred":"source","obj":"DisGeNET"},{"subj":"T11","pred":"source","obj":"DisGeNET"},{"subj":"T12","pred":"source","obj":"DisGeNET"},{"subj":"T13","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_variant_disease","denotations":[{"id":"10191107-4#162#167#geners137852700","span":{"begin":952,"end":957},"obj":"geners137852700"},{"id":"10191107-4#112#119#diseaseC0021294","span":{"begin":902,"end":909},"obj":"diseaseC0021294"}],"relations":[{"id":"162#167#geners137852700112#119#diseaseC0021294","pred":"associated_with","subj":"10191107-4#162#167#geners137852700","obj":"10191107-4#112#119#diseaseC0021294"}],"attributes":[{"subj":"10191107-4#162#167#geners137852700","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"10191107-4#112#119#diseaseC0021294","pred":"source","obj":"DisGeNET5_variant_disease"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"10191107-4#125#129#gene5538","span":{"begin":915,"end":919},"obj":"gene5538"},{"id":"10191107-4#112#119#diseaseC0021294","span":{"begin":902,"end":909},"obj":"diseaseC0021294"},{"id":"10191107-9#166#169#gene5536","span":{"begin":1617,"end":1620},"obj":"gene5536"},{"id":"10191107-9#166#169#gene5538","span":{"begin":1617,"end":1620},"obj":"gene5538"},{"id":"10191107-9#166#169#gene6863","span":{"begin":1617,"end":1620},"obj":"gene6863"},{"id":"10191107-9#220#223#gene5536","span":{"begin":1671,"end":1674},"obj":"gene5536"},{"id":"10191107-9#220#223#gene5538","span":{"begin":1671,"end":1674},"obj":"gene5538"},{"id":"10191107-9#220#223#gene6863","span":{"begin":1671,"end":1674},"obj":"gene6863"},{"id":"10191107-9#111#115#gene1201","span":{"begin":1562,"end":1566},"obj":"gene1201"},{"id":"10191107-9#106#109#diseaseC0027877","span":{"begin":1557,"end":1560},"obj":"diseaseC0027877"}],"relations":[{"id":"125#129#gene5538112#119#diseaseC0021294","pred":"associated_with","subj":"10191107-4#125#129#gene5538","obj":"10191107-4#112#119#diseaseC0021294"},{"id":"166#169#gene5536106#109#diseaseC0027877","pred":"associated_with","subj":"10191107-9#166#169#gene5536","obj":"10191107-9#106#109#diseaseC0027877"},{"id":"166#169#gene5538106#109#diseaseC0027877","pred":"associated_with","subj":"10191107-9#166#169#gene5538","obj":"10191107-9#106#109#diseaseC0027877"},{"id":"166#169#gene6863106#109#diseaseC0027877","pred":"associated_with","subj":"10191107-9#166#169#gene6863","obj":"10191107-9#106#109#diseaseC0027877"},{"id":"220#223#gene5536106#109#diseaseC0027877","pred":"associated_with","subj":"10191107-9#220#223#gene5536","obj":"10191107-9#106#109#diseaseC0027877"},{"id":"220#223#gene5538106#109#diseaseC0027877","pred":"associated_with","subj":"10191107-9#220#223#gene5538","obj":"10191107-9#106#109#diseaseC0027877"},{"id":"220#223#gene6863106#109#diseaseC0027877","pred":"associated_with","subj":"10191107-9#220#223#gene6863","obj":"10191107-9#106#109#diseaseC0027877"},{"id":"111#115#gene1201106#109#diseaseC0027877","pred":"associated_with","subj":"10191107-9#111#115#gene1201","obj":"10191107-9#106#109#diseaseC0027877"}],"attributes":[{"subj":"10191107-4#125#129#gene5538","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-4#112#119#diseaseC0021294","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-9#166#169#gene5536","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-9#166#169#gene5538","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-9#166#169#gene6863","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-9#220#223#gene5536","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-9#220#223#gene5538","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-9#220#223#gene6863","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-9#111#115#gene1201","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10191107-9#106#109#diseaseC0027877","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#dcec93","default":true},{"id":"DisGeNET5_variant_disease","color":"#e293ec"},{"id":"DisGeNET5_gene_disease","color":"#93ecc8"}]}]}}