glutaminase and Chromosome-Deletion

Topics: Chromosome Deletion; Chromosomes, Human, Pair 11; Female; Glucose; Glutaminase; Glutamine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male

Chromosomal abnormalities involving 2q32q33 deletions are very rare and present with a specific phenotype. This case report describes a 37-year-old female patient with 2q32q33 microdeletion syndrome presenting with the characteristic features, but with the addition of secondary cognitive decline. Molecular karyotyping was performed on the patient and her parents. It revealed an 8.6 megabase deletion with the proximal breakpoint in the chromosome band 2q32.2 and the distal breakpoint in 2q33.1. The deletion encompassed 22 known genes, including theGLS,MYO1B,TMEFF2,PGAP1andSATB2genes. The observed deletion was confirmed using a paralogue ratio test. This case report provides further evidence that theSATB2gene, together withGLS,MYO1B,TMEFF2and possiblyPGAP1,is a crucial gene in 2q32q33 microdeletion syndrome. TheSATB2gene seems to be crucial for the behavioural problems noted in our case, but deletion of theGLS,MYO1BandTMEFF2genes presumably contributed to the more complex behavioural characteristics observed. Our patient is also, to our knowledge, the only patient with 2q32q33 microdeletion syndrome with secondary cognitive decline.

Topics: Abnormalities, Multiple; Adult; Aggression; Chromosome Breakpoints; Chromosome Deletion; Chromosomes, Human, Pair 2; Cognitive Dysfunction; Female; Glutaminase; Humans; Hysteria; Intellectual Disability; Karyotyping; Matrix Attachment Region Binding Proteins; Membrane Proteins; Myosin Type I; Neoplasm Proteins; Phenotype; Phosphoric Monoester Hydrolases; Self-Injurious Behavior; Transcription Factors

Three catalytic domains of the Escherichia coli carbamoyl-phosphate synthetase (EC 6.3.5.5) have been identified in previous studies. These include the glutamine amide-N transfer domain in the carboxyl-terminal half of the glutaminase component and at least two adenine nucleotide binding sites in the synthetase component. To delineate the domains involved in subunit interactions, we have examined the effects of deletions and point mutations in the glutaminase and synthetase subunits on formation of the alpha beta holoenzyme. Deletion of the amino-terminal third of the glutaminase subunit abolishes interactions with the synthetase subunit, suggesting that this domain functions to stabilize the complex. Two subunit binding domains have been identified in the synthetase subunit. They are homologous to one another and are located in the amino-terminal and central regions of the synthetase component. These domains are adjacent to regions of the synthetase previously proposed to be involved in ATP binding and, possibly, activation of CO2. The new data enlarge the definition of the structural and functional domains in the two interdependent components of carbamoyl-phosphate synthetase.

Topics: Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); Chromosome Deletion; Chromosome Mapping; Chromosomes, Bacterial; Escherichia coli; Genes, Bacterial; Genotype; Glutaminase; Macromolecular Substances; Mutation; Plasmids; Protein Binding