title: Multi-system disorder syndromes associated with cystinuria type I.
abstract: Cystinuria type I is an autosomal recessive disorder with an exclusively renal phenotype caused by inactivating mutations in SLC3A1. Recently 3 similar but distinct syndromes associated with cystinuria type I have been described: 2p21 deletion syndrome, Hypotonia-Cystinuria Syndrome (HCS) and atypical HCS. Genetic analysis indicated that these are recessive contiguous gene deletion syndromes which differ in the number of genes affected. Patients with HCS are missing both alleles of SLC3A1 and PREPL. In atypical HCS an additional gene (C2orf34) is deleted, and finally, in the 2p21 deletion syndrome the open reading frame of PPM1B is also disrupted. With the exception of SLC3A1, the gene products have not been fully characterized. The severity of the different syndromes reflects the number of genes which are deleted. HCS, a relatively mild syndrome, is characterised by cystinuria type I, generalised hypotonia at birth, growth retardation and minor facial dysmorphic features. On the other end of the spectrum is the 2p21 deletion syndrome, a severe syndrome with a number of additional features including a moderate to severe psychomotor retardation and a decrease in activity of the respiratory chain complexes I, III, IV and V. Finally, atypical HCS displays an intermediate phenotype comparable with classical HCS but associated with mild to moderate mental retardation and a decrease in activity of only the respiratory chain complex IV. This review will focus on the phenotypic similarities and differences observed in these syndromes. Furthermore, we speculate on the function of the gene products, based on the available data.
authors.affiliation: Laboratory for Biochemical Neuroendocrinology, Centre for Human Genetics, University of Leuven, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Martens
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
authors.forename: John W M
authors.initials: JW
authors.lastname: Creemers
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D002889:Chromosomes, Human, Pair 2; D003555:Cystinuria / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D017353:Gene Deletion; D006801:Humans; D009123:Muscle Hypotonia / Q000235:genetics / Q000503:physiopathology; D016366:Open Reading Frames; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D000071636:Protein Phosphatase 2C; D012697:Serine Endopeptidases / Q000235:genetics; D013577:Syndrome
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; C489857:SLC3A1 protein, human; C000607457:PPM1B protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases