Non-type I cystinuria associated with mental retardation and ataxia in a Korean boy with a new missence mutation(G173R) in the SLC7A9 gene

Abstract

Cystinuria is an inherited renal and intestinal disease characterized by defective amino acids reabsorption and cystine urolithiasis. It is unusually associated with neurologic symptoms. Mutations in two genes, SLC3A1 and SLC7A9, have been identified in cystinuric patients. This report presents a 13-yr-old boy with cystinuria who manifested difficulty in walking, ataxia, and mental retardation. Somatosensory evoked potential of posterior tibial nerve stimulation showed the central conduction dysfunction through the posterior column of spinal cord. He was diagnosed non-type I cystinuria by urinary amino acid analysis and oral cystine loading test. We screened him and his family for gene mutation by direct sequencing of SLC3A1 and SLC7A9 genes. In this patient, we identified new missence mutation G173R in SLC7A9 gene.

Keywords: Mutation; Neurologic Manifestations; Non-type I Cystinuria; SLC7A9.

Fig. 1

Pedigree of family with patient that carry mutation in SLC7A9, electropherograms of DNA sequencing for G173R mutation, and the result of oral cystine load in the patient. (A) Pedigree of family with patient; mutation in SLC7A9 and urine dibasic amino acid excretion. Urine amino acid excretion values for cystine (Cys), lysine (Lys), arginine (Arg), and ornithine (Orn) are expressed in µM/g creatinine (normal range: Cys, 30-130; Lys, 150-630; Arg, 30-110; Orn, 30-90). (B) Point mutation G173R (535G→A substitution) in SLC7A9 gene localized in exon 5. Patient's sequence has both G (normal) and A (mutant) at nucleotide 535, resulting in the presence of Gly (codon GGA) and Arg (codon AGA). (C) Changes in plasma cystine level after an oral L-cystine dihydrochloride load of 0.25 mM/kg body weight in the patient.