Structure of the human palmitoyl-protein thioesterase-2 gene (PPT2) in themajor histocompatibility complex on chromosome 6p21.3

Patmitoyl-protein thioesterase-2 (PPT2) is a homolog of PPT1; the enzyme th at is deficient in the lysosomal storage disorder, infantile neuronal ceroi d lipofuscinosis (NCL). As a first step toward determining whether mutation s in the gene encoding PPT2 (PPT2) are associated with any of the molecular ly uncharacterized forms of NCL, we report here the structure and chromosom al localization of human PPT2. PPT2 spans about 10 kb and is composed of ni ne exons. One major (2.0 kb) and two minor (7.0 and 2.8 kb) mRNAs are trans cribed fi om the gene, and the larger transcripts appear to be messenger RN As in which PPT2 exons are spliced into a downstream gene encoding a homolo g of human latent transforming growth factor-p binding protein (human LTBP) . PPT2 is located in the human major histocompatibility class III locus on chromosome 6p21.3, a position that rules out PPT2 as 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 susp ected 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 within PPT2) will ai d in the further delineation of the possible role of PPT2 in lysosomal stor age disorders of unknown etiology. (C) 1999 Academic Press.