title: Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.
abstract: Ocular nonnephropathic cystinosis, a variant of the classic nephropathic type of cystinosis, is an autosomal recessive lysosomal storage disorder characterized by photophobia due to corneal cystine crystals but absence of renal disease. We determined the molecular basis for ocular cystinosis in four individuals. All had mutations in the cystinosis gene CTNS, indicating that ocular cystinosis is allelic with classic nephropathic cystinosis. The ocular cystinosis patients each had one severe mutation and one mild mutation, the latter consisting of either a 928 G-->A (G197R) mutation or an IVS10-3 C-->G splicing mutation resulting in the insertion of 182 bp of IVS10 into the CTNS mRNA. The mild mutations appear to allow for residual CTNS mRNA production, significant amounts of lysosomal cystine transport, and lower levels of cellular cystine compared with those in nephropathic cystinosis. The lack of kidney involvement in ocular cystinosis may be explained by two different mechanisms. On the one hand (e.g. the G197R mutation), significant residual cystinosin activity may be present in every tissue. On the other hand (e.g. the IVS 10-3 C-->G mutation), substantial cystinosin activity may exist in the kidney because of that tissue's specific expression of factors that promote splicing of a normal CTNS transcript. Each of these mechanisms could result in minimally reduced lysosomal cystine transport in the kidneys.
authors.affiliation: Section on Human Biochemical Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Anikster
authors.forename: C
authors.initials: C
authors.lastname: Lucero
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: M
authors.initials: M
authors.lastname: Huizing
authors.forename: V
authors.initials: V
authors.lastname: Shotelersuk
authors.forename: I
authors.initials: I
authors.lastname: Bernardini
authors.forename: G
authors.initials: G
authors.lastname: McDowell
authors.forename: F
authors.initials: F
authors.lastname: Iwata
authors.forename: M I
authors.initials: MI
authors.lastname: Kaiser-Kupfer
authors.forename: R
authors.initials: R
authors.lastname: Jaffe
authors.forename: J
authors.initials: J
authors.lastname: Thoene
authors.forename: J A
authors.initials: JA
authors.lastname: Schneider
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D026921:Amino Acid Transport Systems, Neutral; D001483:Base Sequence; D015152:Blotting, Northern; D003554:Cystinosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers; D005128:Eye Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human; D017931:DNA Primers; D006023:Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger