The Genetic Diversity of Cystinuria in a UK Population of Patients.

[cystinuria]

To examine the genetic mutations in the first UK cohort of patients with cystinuria with preliminary genotype /phenotype correlation PATIENTS AND METHODS : DNA sequencing and MLPA were used to identify the mutations in 74 patients in a specialist cystinuria clinic in the UK . Patients with type A cystinuria were classified into two groups : group M patients had at least one missense mutation . Group N patients had two alleles of all other types of mutations including frameshift , splice site , nonsense , deletions and duplications . The levels of urinary dibasic amino acids , age of presentation of disease , number of stone episodes and interventions were compared between patients in the two groups using Mann-Whitney U test .41 patients had type A cystinuria including one patient with a variant of unknown significance . 23 patients had type B cystinuria , including 6 patients with variants of unknown significance . One patient had 3 sequence variants in SLC 7 A 9 however 2 are of unknown significance . Three patients had type AB cystinuria . Three had a single mutation in SLC 7 A 9 . No identified mutations were found in three patients in either gene . There were a total of 88 mutations in SLC 3 A 1 and 55 mutations in SLC 7 A 9 . There were 23 pathogenic mutations identified in our UK cohort of patients not previously reported in literature . In patients with type A cystinuria , the presence of a missense mutation correlated to lower levels of urinary lysine (611 .9 mM /MC SE 22 .65 vs 752 .3 mM /MC SE 46 .39 , p =0 .0171 ), arginine (194 .8 mM /MC SE 24 .83 vs 397 .7 mM /MC SE 15 .32 , p =0 .0008 ) and ornithine (109 .2 mM /MC SE 7 .403 vs 146 .6 mM /MC SE 12 .7 , p =0 .0211 ). There was no difference in the levels of urinary cystine (182 .1 mM /MC SE 8 .89 vs 207 .2 mM /MC SE 19 .23 , p =0 .2343 ).We have characterised the genetic diversity of cystinuria in a UK population including 23 pathogenic mutations not previously described in literature . Patients with at least one missense mutation in SLC 3 A 1 had significantly lower levels of lysine , arginine , ornithine but not cystine than patients with all other combinations of mutations .