title: A recessive contiguous gene deletion of chromosome 2p16 associated with cystinuria and a mitochondrial disease.
abstract: Deletions ranging from 100 Kb to 1 Mb--too small to be detected under the microscope--may still involve dozens of genes, thus causing microdeletion syndromes. The vast majority of these syndromes are caused by haploinsufficiency of one or several genes and are transmitted as dominant traits. We identified seven patients originating from an extended family and presenting with a unique syndrome, inherited in a recessive mode, consisting of cystinuria, neonatal seizures, hypotonia, severe somatic and developmental delay, facial dysmorphism, and lactic acidemia. Reduced activity of all the respiratory chain enzymatic complexes that are encoded in the mitochondria was found in muscle biopsy specimens of the patients examined. The molecular basis of this disorder is a homozygous deletion of 179,311 bp on chromosome 2p16, which includes the type I cystinuria gene (SLC3A1), the protein phosphatase 2Cbeta gene (PP2Cbeta), an unidentified gene (KIAA0436), and several expressed sequence tags. The extent of the deletion suggests that this unique syndrome is related to the complete absence of these genes' products, one of which may be essential for the synthesis of mitochondrial encoded proteins.
authors.affiliation: Department of Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel. ruthi@bgumail.bgu.ac.il
authors.forename: R
authors.initials: R
authors.lastname: Parvari
authors.forename: I
authors.initials: I
authors.lastname: Brodyansky
authors.forename: O
authors.initials: O
authors.lastname: Elpeleg
authors.forename: S
authors.initials: S
authors.lastname: Moses
authors.forename: D
authors.initials: D
authors.lastname: Landau
authors.forename: E
authors.initials: E
authors.lastname: Hershkovitz
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D026923:Amino Acid Transport Systems, Basic; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003555:Cystinuria / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000503:physiopathology; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D029701:Saccharomyces cerevisiae Proteins; D013577:Syndrome
chemical_list: D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; C499489:SLC7A9 protein, human; D029701:Saccharomyces cerevisiae Proteins; C087358:PTC1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C