title: Mutation of solute carrier SLC16A12 associates with a syndrome combining juvenile cataract with microcornea and renal glucosuria.
abstract: Unobstructed vision requires a particular refractive index of the lens, a measure based on the organization of the structural proteins within the differentiated lens cells. To ensure an intact lens structure, homeostasis within the lens cells is indispensable. Alterations of the lens structure result in opacity and lead to cataract. Renal glucosuria is defined by elevated glucose level in the urine without hyperglycemia and without evidence of morphological renal anomalies. In a Swiss family with autosomal dominant juvenile cataract, microcornea, and renal glucosuria, we have identified a nonsense mutation in a member of the carboxylic acid transporter family SLC16. The underlying gene defect in SLC16A12 resides within a 3 cM region on chromosome 10q23.13 defined by linkage mapping of this phenotype. We found tissue-specific variability of SLC16A12 transcript levels in control samples, with high expression in the eye and kidney, the two organs affected by this syndrome. This report demonstrates biological relevance of this solute carrier. We hypothesize that SLC16A12 is important for lens and kidney homeostasis and discuss its potential role in age-related cataract.
authors.affiliation: Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University Zurich, CH-8603 Schwerzenbach, Switzerland. kloeckener@medgen.unizh.ch
authors.forename: Barbara
authors.initials: B
authors.lastname: Kloeckener-Gruissem
authors.forename: Kristof
authors.initials: K
authors.lastname: Vandekerckhove
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: John
authors.initials: J
authors.lastname: Neidhardt
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Isaak
authors.initials: I
authors.lastname: Schipper
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Berger
mesh_terms: D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D018389:Codon, Nonsense; D003315:Cornea / Q000002:abnormalities*; D005260:Female; D014644:Genetic Variation; D006030:Glycosuria, Renal / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D010375:Pedigree; D013557:Switzerland; D013577:Syndrome; D014158:Transcription, Genetic
chemical_list: D018389:Codon, Nonsense; D027501:Monocarboxylic Acid Transporters; C527548:SLC16A12 protein, human