Identification of a Novel Gene Mutated in Patients With Juvenile Cataract Associated With Microcornea and Glucosuria

Abstract

Purpose: : Identification of a pathogenic mutation in a Swiss family with the novel phenotype of autosomal dominant (ad) juvenile cataract, microcornea and renal glucosuria.

Methods: : Clinical features of patients from a Swiss family affected by juvenile cataract, microcornea and renal glucosuria have been described (Vandekerckhove et al. Klin Monatsbl Augenheilkd 2007). DNAs from affected and unaffected family members were subjected to linkage mapping and sequencing of candidate genes. Expression analyses were performed using RT-PCR experiments.

Results: : Linkage studies identified a 3cM interval on chromosome 10q23 as containing the pathogenic mutation. Several candidate genes were sequenced and a heterozygous premature termination codon mutation was found in the coding region of the monocarboxylate transporter SLC16A12 gene in patients from the Swiss family. RT-PCR experiments of this novel gene indicated tissue-specific regulation of expression with high levels of transcripts in kidney and lens.

Conclusions: : With these experiments we identified a novel gene encoding the monocarboxylate transporter SLC16A12 of until now unknown biological function. Alteration of this protein can lead to the development of ad cataract, microcornea and glucosuria. We are discussing its potenial as risk factor for age-related cataract. The function of the transporter may be relevant for lens and kidney homeostasis.

Keywords: gene mapping • gene/expression • cataract