Nephropathic cystinosis is an autosomal recessive disorder caused by the 
defective transport of cystine out of lysosomes. Recently, the causative gene 
(CTNS) was identified and presumed to encode an integral membrane protein called 
cystinosin. Many of the disease-associated mutations in CTNS are deletions, 
including one >55 kb in size that represents the most common cystinosis allele 
encountered to date. In an effort to determine the precise genomic organization 
of CTNS and to gain sequence-based insight about the DNA within and flanking 
cystinosis-associated deletions, we mapped and sequenced the region of human 
chromosome 17p13 encompassing CTNS. Specifically, a bacterial artificial 
chromosome (BAC)-based physical map spanning CTNS was constructed by 
sequence-tagged site (STS)-content mapping. The resulting BAC contig provided 
the relative order of 43 STSs. Two overlapping BACs, which together contain all 
of the CTNS exons as well as extensive amounts of flanking DNA, were selected 
and subjected to shotgun sequencing. A total of 200,237 bp of contiguous, 
high-accuracy sequence was generated. Analysis of the resulting data revealed a 
number of interesting features about this genomic region, including the 
long-range organization of CTNS, insight about the breakpoints and intervening 
DNA associated with the common cystinosis-causing deletion, and structural 
information about five genes neighboring CTNS (human ortholog of rat vanilloid 
receptor subtype 1 gene, CARKL, TIP-1, P2X5, and HUMINAE). In particular, 
sequence analysis detected the presence of a novel gene (CARKL) residing within 
the most common cystinosis-causing deletion. This gene encodes a previously 
unknown protein that is predicted to function as a carbohydrate kinase. 
Interestingly, both CTNS and CARKL are absent in nearly half of all cystinosis 
patients (i.e., those homozygous for the common deletion). [The sequence data 
described in this paper have been submitted to the GenBank data library under 
accession nos. AF168787 and AF163573.]