Lesch-Nyhan Syndrome, HPRT-Related Hyperuricemia and Gout via the HPRT1 Gene
Summary and Pricing
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture ProbesTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
7129 | HPRT1 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency results in a spectrum of clinical phenotypes which include Lesch-Nyhan syndrome, HPRT1-related hyperuricemia and gout (Fasullo and Endres 2015).
Lesch-Nyhan syndrome is characterized by motor dysfunction, cognitive impairment, behavioral disturbance and hyperuricemia with onset in infancy and childhood. Symptoms of Lesch-Nyhan syndrome include choreoathetosis, variable intellectual disability, cerebral palsy, developmental delay, nephrolithiasis, and persistent self-mutilation which is a hallmark of this disease (Fasullo and Endres 2015). A variable spectrum of neurological involvement occurs predominantly in males. In rare occasions, females may exhibit Lesch-Nyhan syndrome due to skewed inactivation of X chromosomes (Jinnah et al. 2000).
HPRT-related hyperuricemia, in contrast to Lesch-Nyhan syndrome, is due to partial HPRT deficiency with disease onset usually in childhood. Hyperuricemia increases the risk for crystalluria, nephrolithiasis and gout. Resulting renal complications can lead to nephropathy, even renal failure (Srivastava et al 2002; Jinnah et al 2010; Fu et al 2014). Female carriers may develop hyperuricemia later in life.
HPRT-related gout is another consequence of hyperuricemia due to partial HPRT1 deficiency. This type of gout accounts for less than 2% of all adult male patients with gout (Jinnah et al. 2010; Fu and Jinnah 2012).
Genetics
Lesch-Nyhan syndrome and other HPRT1-related disorders are inherited in an X-linked recessive manner and caused by pathogenic variants in the HPRT1 gene encoding hypoxanthine guanine phosphoribosyltransferase. This transferase catalyzes the conversion of hypoxanthine to inosine monophosphate and guanine to guanine monophosphate. This transferase plays a central role in the generation of purine nucleotides through the purine salvage pathway. HPRT1 is the only gene known to be responsible for Lesch-Nyhan syndrome. Pathogenic variants in HPRT1 include missense, nonsense, small deletion and insertion, and splice mutations, as well as large deletions in the HPRT1 locus (Jinnah et al. 2000; Fuh and Jinnah 2012; Fu et al. 2014). De novo pathogenic variants have also been reported (Nyhan et al. 2014).
In the case of HPRT1-related hyperuricemia and gout, genotype-phenotype studies imply that pathogenic variants resulting in little or no residual enzyme function are responsible for classic Lesch-Nyhan syndrome, while pathogenic variants retaining residual enzyme activity manifest HPRT1-related hyperuricemia and gout (Jinnah et al 2010).
Clinical Sensitivity - Sequencing with CNV PG-Select
DNA sequence analysis detects HPRT1 pathogenic variants in ~90 -95% of affected Lesch-Nyhan syndrome males and 80% of female carriers due to germline mosaicism (Nyhan et al. 2014). Sensitivity is not available for HPRT1-related gout.
Testing Strategy
This test provides full coverage of all coding exons of the HPRT1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
HPRT1 sequencing test is recommended for patients with Lesch-Nyhan syndrome. Candidates for HPRT1 testing also include patients with suspected symptoms of HPRT1-related hyperuricemia and gout.
HPRT1 sequencing test is recommended for patients with Lesch-Nyhan syndrome. Candidates for HPRT1 testing also include patients with suspected symptoms of HPRT1-related hyperuricemia and gout.
Gene
Official Gene Symbol | OMIM ID |
---|---|
HPRT1 | 308000 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Name | Inheritance | OMIM ID |
---|---|---|
Gout, HPRT-Related | XL | 300323 |
Lesch-Lyhan Syndrome | XL | 300322 |
Related Test
Name |
---|
Nephrolithiasis and Nephrocalcinosis Panel |
Citations
- Fasullo M., Endres L. 2015. International journal of molecular sciences. 16: 9431-49. PubMed ID: 25923076
- Fu R. et al. 2014. Molecular genetics and metabolism. 112: 280-5. PubMed ID: 24930028
- Fu R., Jinnah HA. 2012. The Journal of Biological Chemistry. 287: 2997-3008 PubMed ID: 22157001
- Jinnah H. A. et al. 2010. Brain. 133: 671-689 PubMed ID: 20176575
- Jinnah HA. et al. 2000. Mutation research. 463: 309-26. PubMed ID: 11018746
- Nyhan WL et al. 2014. Lesch-Nyhan Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Bean JJH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301328
- Srivastava T. et al. 2002. American journal of medical genetics. 108: 219-22. PubMed ID: 11891689
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
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.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
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.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.