The Invitae Cystinuria Panel analyzes 3 genes that are associated with cystinuria, a disorder affecting the reabsorption of certain amino acids, including cystine in the kidney and bladder. This panel is intended for individuals suspected to have cystinuria based on clinical symptoms and/or elevated urinary cystine levels. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Additionally, identification of disease-causing variants provides accurate genetic counseling and reproductive risks, risk assessment and carrier status of at-risk relatives.
PREPL SLC3A1 SLC7A9
PREPL SLC3A1 SLC7A9
Cystinuria is associated with a predisposition to developing cystine stones in the kidneys, bladder, and ureters. Symptoms of stone development include nausea, flank pain, hematuria, recurrent urinary tract infections and, rarely, renal failure. Stones typically develop in the third decade of life but may present in individuals as young as 2 years of age; the lifetime risk is 50% with a high likelihood of bilateral stone formation. Affected individuals are characterized by abnormally high levels of urinary cystine. Individuals with a single pathogenic variant are typically asymptomatic but may still manifest with elevated urine cystine levels.
Individuals with deletions in both SLC3A1 and PREPL present with cystinuria and severe hypotonia (Prader-Willi like syndrome).
For individuals with clinical symptoms of cystinuria described to date, 100% had pathogenic variants in SLC3A1, SLC7A9, or both.
Cystinuria is autosomal recessive, although individuals with heterozygous pathogenic variants have also been reported to have elevated urinary cystine.
Globally, the prevalence of cystinuria is estimated at 1 in 7,000, although it can range from as high as 1 in 2,500 to as low as 1 in 100,000 across different ethnic groups.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|
PREPL: Only deletion/duplication analysis is offered for this gene.