Cystinosis via the CTNS Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
1561 CTNS$810.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Sanger sequencing combined with the common 57 kb deletion test will detect pathogenic variants in 85-95% of patients who present with typical cystinosis symptoms. In a cohort of 12 Turkish patients, 92% of patients had a molecular diagnosis detectable by these methods (Topaloglu et al. 2012). In another study of 13 Egyptian patients, 85% had identifiable pathogenic variants (Soliman et al. 2014). In people of Northern European ancestry, approximately 50% of patients with nephropathic cystinosis are homozygous for the 57 kb deletion (Nesterova and Gahl 2014). In addition to the common 57 kb deletion, a number of other gross deletions in CTNS have been reported to be causative for cystinosis.

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Clinical Features

Cystinosis is a condition characterized by the accumulation of the amino acid cystine within the lysosomes of cells. Excess cystine in cells results in crystal formation which is damaging to many organs and tissues. In particular, the kidneys and eyes of individuals with cystinosis are especially vulnerable. Children with cystinosis are normal at birth, but develop signs of renal tubular Fanconi syndrome between 6 and 12 months of age (Nesterova and Gahl 2014; Gahl and Thoene 2014). Symptoms include failure to thrive, vomiting, acidosis, polyuria, excessive thirst, dehydration, electrolyte imbalances and hypophosphatemic rickets (Gahl and Thoene 2014). If left untreated, the major clinical manifestation is renal failure at around 9-10 years of age (Nesterova and Gahl 2014). Corneal cystine crystals can cause photophobia which is always present by two years of age. An intermediate form of cystinosis can also occur, but typically onset is not until adolescence, and symptoms are not as severe. Ocular cystinosis (non-nephropathic) presents with photophobia, but cystine crystals are present in the bone marrow and conjunctiva as well as the corneas. Diagnosis is typically made on a routine eye exam with a slit lamp. Cystine depletion therapy with cysteamine bitartrate can reduce 90% of cysteine content in cells. With early, diligent treatment, end stage renal disease can be delayed or even prevented (Nesterova and Gahl 2014). Supplementation with phosphate, vitamin D, and good nutrition will reduce growth deficiencies and prevent hypophosphatemic rickets (Nesterova and Gahl 2014). Prior to the use of renal transplant and cystine depletion therapy, the nephropathic patient lifespan was no longer than ten years. With these therapies, affected individuals can survive into forties and fifties.


Cystinosis is an autosomal recessive disorder caused by pathogenic variants in the CTNS gene located on chromosome 17p13.2. CTNS encodes the cystinosin protein (327 amino acids) which transports cystine out of the lysosome into the cytoplasm. It contains seven transmembrane domains and two lysosomal targeting motifs. CTNS is the only gene which is associated with cystinosis. The incidence of infantile nephropathic cystinosis is approximately 1 per 100,000 to 200,000 live births (Levtchenko et al. 2014). The French region of Brittany has a higher incidence of 1 per 26,000. The most common pathogenic variant is a 57 kb deletion which includes exons 1-9 and part of exon 10 (Levtchenko et al. 2014; Touchman et al. 2000). In people of Northern European ancestry, approximately 50% of patients with nephropathic cystinosis are homozygous for the 57 kb deletion (Nesterova and Gahl 2014). Other pathogenic variants include missense, nonsense, splice site variants, insertions, and deletions (Human Gene Mutation Database). The missense variants are typically present in the transmembrane region of the cystinosin protein.

Testing Strategy

Testing is accomplished by PCR amplification from genomic DNA and bidirectional Sanger sequencing of all coding exons of the CTNS gene and ~10bp of adjacent noncoding sequences. This testing strategy will reveal coding sequence changes, splice site mutations and small insertions or deletions in the CTNS gene, but will not detect large duplications or deletions of the CTNS locus. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known pathogenic variants or to confirm research results. Testing for the common 57 kb deletion can be ordered separately through test code #1636.

This testing also includes coverage for the c.-520G>T, c.-512G>C and c.141-24T>C pre-coding or intronic variants, as well as ~10 bp of adjacent sequence.

Indications for Test

Candidates for this test are patients with symptoms consistent with cystinosis and increased cystine levels in polymorphonuclear leukocytes. Testing is also indicated for family members of patients who have known CTNS pathogenic variants.


Official Gene Symbol OMIM ID
CTNS 606272
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Cystinosis via the CTNS Gene, 57-kb Deletion
Neonatal Crisis Sequencing Panel with CNV Detection


Genetic Counselors
  • Gahl W.A., Thoene J.G. 2014. Cystinosis: A Disorder of Lysosomal Membrane Transport. OMMBID - The Online Metabolic and Molecular Bases of Inherited Diseases., New York, NY: The McGraw-Hill Companies, Inc.
  • Human Gene Mutation Database (Bio-base).
  • Levtchenko E., van den Heuvel L., Emma F., Antignac C. 2014. Clinical utility gene card for: Cystinosis. European Journal of Human Genetics 22:5. PubMed ID: 24045844
  • Nesterova, G., Gahl, WA. 2014. Cystinosis. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301574
  • Soliman NA, Elmonem MA, Heuvel L van den, Hamid RHA, Gamal M, Bongaers I, Marie S, Levtchenko E. 2014. Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis. JIMD Rep. PubMed ID: 24464559
  • Topaloglu R, Vilboux T, Coskun T, Ozaltin F, Tinloy B, Gunay-Aygun M, Bakkaloglu A, Besbas N, van den Heuvel L, Kleta R, Gahl WA. 2012. Genetic basis of cystinosis in Turkish patients: a single-center experience. Pediatr Nephrol 27: 115–121. PubMed ID: 21786142
  • Touchman J.W., Anikster Y., Dietrich N.L., Maduro V.V.B., McDowell G., Shotelersuk V., Bouffard G.G., Beckstrom-Sternberg S.M., Gahl W.A., Green E.D. 2000. The Genomic Region Encompassing the Nephropathic Cystinosis Gene (CTNS): Complete Sequencing of a 200-kb Segment and Discovery of a Novel Gene within the Common Cystinosis-Causing Deletion. Genome Res 10: 165–173. PubMed ID: 10673275
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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