Ocular nonnephropathic cystinosis, a variant of the classic nephropathic type of 
cystinosis, is an autosomal recessive lysosomal storage disorder characterized 
by photophobia due to corneal cystine crystals but absence of renal disease. We 
determined the molecular basis for ocular cystinosis in four individuals. All 
had mutations in the cystinosis gene CTNS, indicating that ocular cystinosis is 
allelic with classic nephropathic cystinosis. The ocular cystinosis patients 
each had one severe mutation and one mild mutation, the latter consisting of 
either a 928 G-->A (G197R) mutation or an IVS10-3 C-->G splicing mutation 
resulting in the insertion of 182 bp of IVS10 into the CTNS mRNA. The mild 
mutations appear to allow for residual CTNS mRNA production, significant amounts 
of lysosomal cystine transport, and lower levels of cellular cystine compared 
with those in nephropathic cystinosis. The lack of kidney involvement in ocular 
cystinosis may be explained by two different mechanisms. On the one hand (e.g. 
the G197R mutation), significant residual cystinosin activity may be present in 
every tissue. On the other hand (e.g. the IVS 10-3 C-->G mutation), substantial 
cystinosin activity may exist in the kidney because of that tissue's specific 
expression of factors that promote splicing of a normal CTNS transcript. Each of 
these mechanisms could result in minimally reduced lysosomal cystine transport 
in the kidneys.