title: CTNS mutations in African American patients with cystinosis.
abstract: Cystinosis, an autosomal recessive lysosomal storage disorder, is rarely diagnosed in African Americans. The disease results from mutations in the gene CTNS; at least 55 such mutations have been reported. By far the most common is a 57,257-bp deletion of Northern European origin encompassing most of the CTNS gene. We performed mutation analysis on DNA from four African American patients with cystinosis. In one individual with classical, nephropathic cystinosis, we identified a new molecular defect, i.e., a homozygous GT-->CC substitution at the +5 position of IVS 5 of CTNS (IVS 5+5 GT-->CC). The out-of-frame splicing of exon 5 creates a null allele consistent with the patient's severe phenotype. Two patients were heterozygous and one homozygous for the common 57-kb deletion allele, reflecting the admixture of African and Northern European gene pools in North America. The two African Americans heterozygous for the 57-kb deletion were also hemizygous for a 928G-->A change, associated with ocular or nonnephropathic cystinosis. These two individuals are the only known African Americans with ocular cystinosis. We conclude that the diagnosis of cystinosis should be entertained in African Americans with symptoms of the disease, and that mutation analysis for the 57-kb deletion should be considered in this group of patients.
authors.affiliation: Section on Human Biochemical Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development/NIH, 10 Center Drive, Building 10, Bethesda, MD 20892, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kleta
authors.forename: Y
authors.initials: Y
authors.lastname: Anikster
authors.forename: C
authors.initials: C
authors.lastname: Lucero
authors.forename: V
authors.initials: V
authors.lastname: Shotelersuk
authors.forename: M
authors.initials: M
authors.lastname: Huizing
authors.forename: I
authors.initials: I
authors.lastname: Bernardini
authors.forename: M
authors.initials: M
authors.lastname: Park
authors.forename: J
authors.initials: J
authors.lastname: Thoene
authors.forename: J
authors.initials: J
authors.lastname: Schneider
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000293:Adolescent; D000483:Alleles; D026921:Amino Acid Transport Systems, Neutral; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003554:Cystinosis / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006023:Glycoproteins; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009154:Mutation; D020125:Mutation, Missense; D001741:Black or African American
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human; D018076:DNA, Complementary; D006023:Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D004247:DNA