title: The 2p21 deletion syndrome: characterization of the transcription content.
abstract: The vast majority of small-deletion syndromes are caused by haploinsufficiency of one or several genes and are transmitted as dominant traits. We have previously identified a homozygous deletion of 179,311 bp on chromosome 2p21 as the cause of a unique syndrome, inherited in a recessive mode, consisting of cystinuria, neonatal seizures, hypotonia, severe somatic and developmental delay, facial dysmorphism, and reduced activity of all the respiratory chain enzymatic complexes that are encoded in the mitochondria. We now present the transcription content of this region: Multiple splicing variants of the genes protein phosphatase 1B (formerly 2C) magnesium-dependent, beta isoform (PPM1B), SLC3A1, and KIAA0436 (approved gene symbol PREPL) were identified and their patterns of expression analyzed. The spliced variants are predicted to have additional functions compared to the known variants and their patterns of expression fit the tissues affected by the syndrome. The first exon of an additional gene (C2orf34) is encoded in the deleted region and the gene is not expressed in the patients. In addition several transcripts with very short open reading frames are also encoded in the deletion. The identification of all transcripts encoded in the region deleted in the patients is the first step in the study of the genotype-phenotype correlation of the 2p21 patients.
authors.affiliation: Department of Developmental Molecular Genetics, Soroka Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel. ruthi@bgumail.bgu.ac.il
authors.forename: Ruti
authors.initials: R
authors.lastname: Parvari
authors.forename: Yael
authors.initials: Y
authors.lastname: Gonen
authors.forename: Ismael
authors.initials: I
authors.lastname: Alshafee
authors.forename: Sophia
authors.initials: S
authors.lastname: Buriakovsky
authors.forename: Kfir
authors.initials: K
authors.lastname: Regev
authors.forename: Eli
authors.initials: E
authors.lastname: Hershkovitz
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2; D003555:Cystinuria / Q000235:genetics; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004579:Electron Transport; D005091:Exons; D020224:Expressed Sequence Tags; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D020033:Protein Isoforms; D054645:Protein Phosphatase 1; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D020033:Protein Isoforms; D012313:RNA; D004247:DNA; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1