Cabezas X-Linked Mental Retardation Syndrome via the CUL4B 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 | |
|---|---|---|---|---|---|
| 15155 | CUL4B | 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
Variants in the CUL4B gene cause a form of X-linked mental retardation (XLMR) with short stature, small testes, muscle wasting, and tremor (OMIM 300354) (Cabezas et al. J Med Genet 37:663-668, 2000). Other clinical features include prominent lower lip, kyphosis, joint hyperextensibility, abnormal gait, decreased fine motor coordination, relative macrocephaly, central obesity, unprovoked aggressive outbursts, and small, high-arched feet with wide sandal-gap toes (Tarpey et al. Am J Hum Genet 80:345-352, 2007). Speech delay may also be evident beginning in childhood, and adults may have absent or very limited speech.
Genetics
Cabezas syndrome is inherited in an X-linked recessive manner. The CUL4B gene encodes cullin 4B, a scaffold protein which forms a complex that functions as an E3 ubiquitin ligase. Affected males have the common feature of mental retardation in addition to variable presentation of the features listed above. In obligate carrier females, Zou et al. (Am J Hum Genet 80:561-566, 2007) found a strong selection against cells expressing the mutant allele, resulting in an extremely skewed X-inactivation pattern. Consistent with this observation, obligate carriers have been found to be essentially normal (Tarpey et al. Am J Hum Genet 80:345-352, 2007).
Clinical Sensitivity - Sequencing with CNV PG-Select
A systematic variant screening strategy found CUL4B variants in eight of 250 families with X-linked MR in which chromosomal and FMR1 abnormalities had been ruled-out (Tarpey et al. Am J Hum Genet 80:345-352, 2007). These authors suggest CUL4B variants may account for 3% of all XLMR, thus making it the second most frequent cause of this heterogeneous and common disorder.
Testing Strategy
This test is performed using Next-Generation sequencing with additional Sanger sequencing as necessary.
This test provides full coverage of all coding exons of the CUL4B gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Males with MR and speech delay, who have family histories consistent with X-linked recessive inheritance. Adult males with MR and absent or very limited speech.
Males with MR and speech delay, who have family histories consistent with X-linked recessive inheritance. Adult males with MR and absent or very limited speech.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| CUL4B | 300304 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Mental Retardation, X-Linked, With Short Stature, Hypogonadism, And Abnormal Gait | 300354 |
Citations
- Cabezas, D. A., et.al. (2000). "A new X linked mental retardation (XLMR) syndrome with short stature, small testes, muscle wasting, and tremor localises to Xq24-q25." J Med Genet 37(9): 663-8. PubMed ID: 10978355
- Tarpey, P. S., et.al. (2007). "Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor." Am J Hum Genet 80(2): 345-52. PubMed ID: 17236139
- Tarpey, P. S., et.al. (2007). "Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor." Am J Hum Genet 80(2): 345-52. PubMed ID: 17236139
- Tarpey, P. S., et.al. (2007). "Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor." Am J Hum Genet 80(2): 345-52. PubMed ID: 17236139
- Zou, Y., et.al. (2007). "Mutation in CUL4B, which encodes a member of cullin-RING ubiquitin ligase complex, causes X-linked mental retardation." Am J Hum Genet 80(3): 561-6. PubMed ID: 17273978
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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