The locus for autosomal dominant renal Fanconi Syndrome maps to the long arm of chromosome 15

Familial renal Fanconi Syndrome is a genetic model for the study of the pathophysiology of renal tubular transport. Affected individuals are normal at birth. However, during the second decade of life they develop polyuria, and loss of proximal tubular function results in rickets. With increasing age, these individuals may develop renal failure. Therapy for renal Fanconi syndrome consists of symptomatic supplementation therapy, dialysis, and kidney transplantation. The isolation of the affected gene should initially facilitate postnatal and prenatal diagnosis of renal Fanconi syndrome. Long term, the isolation of this gene and its gene product will allow the study of the pathophysiology of renal Fanconi syndrome. Such studies should lead to a better understanding and consequently a better treatment of this entity. Through knowledge about the pathophysiology of this disorder new drugs may be developed to treat renal tubular transport disorders. We were able to map the locus for autosomal dominant familial renal Fanconi syndrome to the long arm of human chromosome 15 by genotyping a large central Wisconsin pedigree by performing a whole genome scan with 367 highly polymorphic simple sequence repeat (SSR) markers. A maximum LOD score of 3.01 was calculated using the LINKAGE program package (version 5.03), with the analyses conducted assuming a fully penetrant autosomal dominant mode of inheritance. Analysis of an additional 29 markers flanking D15S659 has narrowed the interval to about 3 cM, with the highest LOD observed being 4.43. The fine mapping of the locus for autosomal dominant renal Fanconi Syndrome is continuing, the goal of which is to sufficiently narrow the region to allow the isolation of the associated gene through a positional cloning approach.