Joubert and Meckel-Gruber Syndromes via the RPGRIP1L Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 15289 | RPGRIP1L | 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
Joubert syndrome (JS) (OMIM 213300) is marked by ataxia, hypotonia, abnormal ocular movements, apraxia, neonatal respiratory anomalies, mental retardation, agenesis/hypoplasia of the cerebellar vermis, and a brain malformation known as the "molar tooth sign" (MTS) on cranial MRI. JS patients have substantial phenotypic variation. MTS is considered to be the most characteristic diagnostic feature. Some JS patients develop retinal dystrophy or progressive renal failure. For more information, see Parisi and Glass (GeneReviews, 2007). Meckel-Gruber syndrome (MKS; OMIM 249000) is characterized by occipital encephalocele, polycystic kidneys, hepatic developmental defects, and postaxial polydactyly (Alexiev et al. Arch Pathol Lab Med 130:1236-1238, 2006). MKS is a common cause of prenatal echogenic kidneys (Chaumoitre et al. Ultrasound Obstet Gynecol 28:911-917, 2006). Nearly all MKS infants are stillborn or die shortly after birth.
Genetics
JS and MKS both exhibit autosomal recessive inheritance. Both disorders have high levels of locus heterogeneity with 7 JS genes (TMEM67/MKS3, AHI1, CC2D2A, CEP290, RPGRIP1L, ARL13B, and NPHP1) and 5 MKS genes (MKS1, TMEM67/MKS3, CC2D2A, CEP290, and RPGRIP1L) identified to date. Additional genes are likely to be identified in future. Both JS and MKS are ciliopathies, meaning that they are caused by variants in genes that encode proteins involved in cilia or centrosome structure and function (Hildebrandt and Otto Nat Rev Genet 6:928-940, 2005; www.ciliaproteome.org).
Clinical Sensitivity - Sequencing with CNV PG-Select
The following are the approximate fractions of patients with variants in the indicated genes for Joubert syndrome: CEP290 10%, AHI1 10%, TMEM67/MKS3 10%, CC2D2A 10%, RPGRIP1L 2%, ARL13B 2%, and NPHP1 2% (Parisi et al. 2007). The numbers for MKS are approximately CEP290 10%, MKS1 c.15%, TMEM67/MKS3 15%, CC2D2A 10%, and RPGRIP1L 2%.
Testing Strategy
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This test provides full coverage of all coding exons of the RPGRIP1L gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this test are patients with symptoms consistent with JS or MKS and family members of patients who have known variants. Conclusive connections between clinical features and individual mutated genes have not yet been made. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RPGRIP1L.
Candidates for this test are patients with symptoms consistent with JS or MKS and family members of patients who have known variants. Conclusive connections between clinical features and individual mutated genes have not yet been made. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RPGRIP1L.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| RPGRIP1L | 610937 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Joubert Syndrome 7 | AR | 611560 |
| Meckel Syndrome 5 | AR | 611561 |
Citations
- Alexiev BA, Lin X, Sun CC, Brenner DS. 2006. Meckel-Gruber syndrome: pathologic manifestations, minimal diagnostic criteria, and differential diagnosis. Arch. Pathol. Lab. Med. 130: 1236-1238. PubMed ID: 16879033
- Chaumoitre K, Brun M, Cassart M, Maugey-Laulom B, Eurin D, Didier F, Avni EF. 2006. Differential diagnosis of fetal hyperechogenic cystic kidneys unrelated to renal tract anomalies: A multicenter study. Ultrasound Obstet Gynecol 28: 911–917. PubMed ID: 17094077
- Parisi M, Glass I. 2013. Joubert Syndrome and Related Disorders. 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: 20301500
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
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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