Spectrum of mutations in cystinuria patients presenting with prenatal hyperechoic colon

Cystinuria is a heterogeneous, rare but important cause of inherited kidney stone disease due to mutations in 2 genes: SLC3A1 and SLC7A9. Antenatal hyperechoic colon (HEC) has been reported in some patients as a non-pathological consequence of the intestinal transport defect. We report 83 patients affected by cystinuria: 44 presented prenatally with a HEC (HEC group) and 39 with a classical postnatal form (CC group). SLC3A1 and SLC7A9 were sequenced. All patients were fully genotyped, and the relationship between the genotype and clinical features was analyzed. We identified mutations in SLC3A1 in 80% of the HEC group and in only 49% of the CC group. The SLC3A1 p.Thr216Met mutation was found in 21% of the alleles in the HEC group but was never found in the CC group. Most of the mutations found in the HEC group were considered severe mutations in contrast with the CC group. Twenty-five novel mutations were reported. This study shows a relationship between genotype and the clinical form of cystinuria, suggesting that only the patients with the most severe mutations presented with an HEC. These results emphasized the need for prenatal cystinuria screening using classical third-trimester ultrasound scan and the early management of suspected newborns.