Home
HelpTest ID: 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.
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
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 3 genes associated with cystinuria: SLC3A1, SLC7A9, and PREPL. See Targeted Genes and Methodology Details for Cystinuria Gene Panel and Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for cystinuria.
Method Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.
Reporting Name
Cystinuria Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
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.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
2. PalacÃn M, Goodyer P, Nunes V, et al: Cystinuria. In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease: McGraw-Hill; 2019. Accessed January 07, 2020. Available at http://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225555540
3. Eggermann T, Spengler S, Venghaus A, et al: 2p21 Deletions in hypotonia-cystinuria syndrome. Eur JMed Genet. 2012;55(10)561-563
4. Regal L, Shen XM, Selcen D, et al: PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. Neurology. 2014;82(14)1254-1260
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
Report Available
21 to 28 daysReflex 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.
mcl-moltechtestmenu