Program Nr: 1427 for the 2006 ASHG Annual Meeting

Iminoglycinuria: Molecular findings. R. Kleta1, T. Coskun2, B. Tinloy1, H.I. Aydin2, M. Gunay-Aygun1, H. Stanescu1, I. Bernardini1, W.A. Gahl1. 1) SHBG, MGB, NHGRI, NIH, Bethesda, MD, USA; 2) Department of Pediatrics, Division of Pediatric Nutrition & Metabolism, Hacettepe University Faculty of Medicine, Ankara, Turkey.
   Disorders such as cystinuria (basic aminoaciduria) and Hartnup disorder (neutral aminoaciduria) have been instrumental in identifying the genes responsible for renal tubular transport of amino acids at the plasma membrane level. For iminoglycinuria, candidate genes like SLC6A20 and SLC36A1 have been proposed to be causative. This is because heterologous expression studies have shown that their gene products mediate uptake of proline and glycine, two of the amino acids improperly handled by the proximal tubules of individuals with iminoglycinuria. We identified two patients with iminoglycinuria by serum and urine amino acid analyses showing typically elevated fractional excretions of glycine, proline and hydroxyproline only. Sequencing of all coding exons (including the splice sites) of SLC6A20 and SLC36A1 showed no disease-causing mutations. Based on homology, expression, and function, another member of the SLC36 family, SLC36A2, was selected as a candidate gene for iminoglycinuria. Sequencing of all coding exons of SLC36A2 also revealed no disease-causing mutations. We conclude that amino acid transport genes other than the proposed candidates might be responsible for iminoglycinuria. We are pursuing patients and active collaborations to elucidate the basic genetic defect in iminoglycinuria.