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Identification of three novel mutations of the palmitoyl‐protein thioesterase‐1 ( PPT1 ) gene in children with neuronal ceroid‐lipofuscinosis
Author(s) -
Waliany Sophie,
Das Amit K.,
Gaben Ahmad,
Wisniewski Krystyna E.,
Hofmann Sandra L.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(200002)15:2<206::aid-humu14>3.0.co;2-l
Subject(s) - biology , missense mutation , genetics , allele , mutation , gene , neuronal ceroid lipofuscinosis , phenotype , compound heterozygosity , thioesterase , microbiology and biotechnology , biosynthesis
Eight unrelated children with progressive neurological deterioration and granular osmiophilic deposits (GROD) due to an underlying palmitoyl‐protein thioesterase deficiency were analyzed for mutations in the PPT1 gene. Three novel mutations (G118D, Q291X and F84del) were identified. The novel Q291X mutation was observed in an African‐American child. The G118D and Q291X mutations occurred in infantile‐onset subjects. These two mutations would be predicted to have severe effects on enzyme activity. The novel F84del mutation involves an invariant phenylalanine residue. A missense mutation, Q177E, occurred in three subjects from two families with late‐infantile NCL, confirming an association of the Q177E mutation with a late‐infantile phenotype. Other previously described mutations were R151X (5/16 alleles), T75P (3/16 alleles), R164X (1/16 alleles), and V181M (1/16 alleles). The current study expands the spectrum of mutations in PPT1 deficiency and further confirms the broad range of age of onset of symptoms resulting from an enzyme deficiency previously associated only with infantile NCL. Hum Mutat 15:206–207, 2000. © 2000 Wiley‐Liss, Inc.