Structure of the Human Palmitoyl-Protein Thioesterase-2 Gene (PPT2) in the Major Histocompatibility Complex on Chromosome 6p21.3

• Published in: Genomics (San Diego, Calif.) Calif.), 1999-03, Vol.56 (2), p.208-216
• Main Authors: Soyombo, Abigail A., Yi, Won, Hofmann, Sandra L.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Chromosomes, Human, Pair 6 - genetics; DNA - chemistry; DNA - genetics; Exons; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes - genetics; Genes. Genome; Humans; Infant; Introns; Isoenzymes - genetics; Major Histocompatibility Complex - genetics; Microsatellite Repeats; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutation; Neuronal Ceroid-Lipofuscinoses - enzymology; Neuronal Ceroid-Lipofuscinoses - genetics; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Promoter Regions, Genetic; RNA, Messenger - genetics; RNA, Messenger - metabolism; Thiolester Hydrolases - genetics; Tissue Distribution
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1998.5703

Palmitoyl-protein thioesterase-2 (PPT2) is a homolog of PPT1, the enzyme that is deficient in the lysosomal storage disorder, infantile neuronal ceroid lipofuscinosis (NCL). As a first step toward determining whether mutations in the gene encoding PPT2 (PPT2) are associated with any of the molecularly uncharacterized forms of NCL, we report here the structure and chromosomal localization of humanPPT2. PPT2spans about 10 kb and is composed of nine exons. One major (2.0 kb) and two minor (7.0 and 2.8 kb) mRNAs are transcribed from the gene, and the larger transcripts appear to be messenger RNAs in whichPPT2exons are spliced into a downstream gene encoding a homolog of human latent transforming growth factor-β binding protein (human LTBP).PPT2is located in the human major histocompatibility class III locus on chromosome 6p21.3, a position that rules outPPT2as the causative gene in any of the NCLs at defined chromosomal loci. No mutations were detected by SSCP analysis in a preliminary analysis of 12 subjects referred with a suspected diagnosis of infantile NCL who had normal PPT activity. However, five single nucleotide polymorphisms were found in unrelated normal individuals. These polymorphisms (and a microsatellite discovered withinPPT2) will aid in the further delineation of the possible role ofPPT2in lysosomal storage disorders of unknown etiology.