Sign in →

Test Code CYSGP Cystinuria Gene Panel, Varies


Ordering Guidance


The recommended first-tier test to screen for cystinuria is urinary measurement of cystine, lysine, ornithine, and arginine; order either CYSQN / Cystinuria Profile, Quantitative, 24 Hour, Urine or CYSR / Cystinuria Profile, Quantitative, Random, Urine.

 

Customization of this panel and single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

 

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblast

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

2. For collection instructions, see Blood Spot Collection Instructions

3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)

4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing  (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527)

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Secondary ID

608027

Useful For

Follow up for abnormal biochemical results suggestive of cystinuria

 

Establishing a molecular diagnosis for patients with cystinuria

 

Identifying variants within genes known to be associated with cystinuria, allowing for predictive testing of at-risk family members

Disease States

  • Cystinuria

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

Reporting Name

Cystinuria Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Cystinuria is an inborn error of metabolism resulting from poor absorption and reabsorption of the amino acid cystine in the intestines and kidneys. This leads to an accumulation of poorly soluble cystine and dibasic amino acids (lysine, arginine, and ornithine) in the urine and results in the production of kidney stones (urolithiasis). Symptoms may include acute episodes of abdominal or lower back pain, presence of blood in the urine (hematuria), and recurrent episodes of kidney stones may result in frequent urinary tract infections, which may ultimately result in renal insufficiency. The combined incidence of cystinuria has been estimated to be 1 in 7000.

 

Cystinuria is an autosomal recessive disease, but some heterozygous carriers have an autosomal dominant, incomplete penetrance appearance with elevated, but typically benign, urinary cystine and dibasic amino acid excretion. Some heterozygotes do tend to have higher levels of lysine and cystine versus arginine and ornithine as compared to patients with homozygous variants, who excrete large amounts of cysteine and all 3 dibasic amino acids.

 

Cystinuria is caused by variants in genes, SLC3A1 and PREPL on chromosome 2p and SLC7A9 on chromosome 19q. Initially, the disease was classified into subtypes I, II, and III (type II and III are also referred as nontype I) based on the amount of urinary cystine excreted in heterozygous parental specimens. A new classification system has been proposed to distinguish the various forms of cystinuria: type A, due to variants in the SLC3A1 gene; type B, due to variants in the SLC7A9 gene; and type AB, due to 1 variant in each SLC3A1 and SLC7A9 gene.

 

A contiguous gene deletion involving both SLC3A1 and PREPL gene is associated with an autosomal recessive hypotonia-cystinuria syndrome, presenting with dysmorphic features, severe neonatal hypotonia, myasthenic syndrome, failure to thrive in infancy with transition to hyperphagia in late childhood, and nephrolithiasis with excretion of cystine, lysine, arginine, and ornithine. Variants in the PREPL gene are associated with autosomal recessive congenital myasthenic syndrome 22 (CMS22), which does not present with cystinuria.

 

Urinary measurement of cystine, lysine, ornithine, and arginine (CYSQN / Cystinuria Profile, Quantitative, 24 Hour, Urine or CYSR / Cystinuria Profile, Quantitative, Random, Urine) is recommended as a first-tier test to screen for cystinuria prior to molecular genetics testing.

 

Treatment/management options for cystinuria include a high fluid intake, alkali and dietary modifications, and administration of oral tiopronin to prevent formation of cystine stones.

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing  variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated to be over 99% for single nucleotide variants, over 94% for insertions/deletions (indels) less than 40 base pairs (bp), over 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Cystinuria Gene Panel for details regarding targeted genes analyzed and the specific gene regions not routinely covered.(Unpublished Mayo method)

 

Genes analyzed: SLC3A1, SLC7A9, and PREPL.

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81479

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CYSGP Cystinuria Gene Panel 105260-4

 

Result ID Test Result Name Result LOINC Value
608728 Test Description 62364-5
608729 Specimen 31208-2
608730 Source 31208-2
608731 Result Summary 50397-9
608732 Result 82939-0
608733 Interpretation 69047-9
608734 Resources 99622-3
608735 Additional Information 48767-8
608736 Method 85069-3
608737 Genes Analyzed 48018-6
608738 Disclaimer 62364-5
608739 Released By 18771-6

Day(s) Performed

Varies

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.