Microcephaly, Lymphedema, and Chorioretinal Dysplasia (MLCRD) / Chorioretinal Dysplasia, Microcephaly, and Mental Retardation (CDMMR) / Familial Exudative Vitreoretinopathy (FEVR) via the KIF11 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11425 | KIF11 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.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
Microcephaly, primary lymphedema, and chorioretinal dysplasia (MLCRD) is inherited in an autosomal dominant manner with lymphedema that is typically confined to the dorsa of the feet (Ostergaard et al. 2012). Patients display mild to severe microcephaly with characteristic facial features including palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, and prominent chin and ears. Eye abnormalities may or may not be present and include chorioretinopathy, retinal folds, micropthalmia, and astigmatism. Features of MLCRD overlap those of chorioretinal dysplasia, microcephaly, and mental retardation (CDMMR) and Familial Exudative Vitreoretinopathy (FEVR) and it has been suggested that all three disorders represent a single disorder with a broad spectrum of clinical features (Ostergaard et al. 2012; Hazan et al. 2012; Jones et al. 2014; Mirzaa et al. 2014; Robitaille et al. 2014).
Genetics
MLCRD, CDMMR, and FEVR are caused by pathogenic variants in the KIF11 gene and are inherited in an autosomal dominant manner. KIF11 encodes kinesin family member 11 (EG5), a spindle motor protein (Valentine et al. 2006). Kinesins have an N-terminal motor domain, microtubule binding domain, and ATP binding site for ATPase activity. Members of the kinesin protein family are involved in trafficking along microtubules during such cellular functions as axonal transport, chromosomal disjunction during meiosis and mitosis, and movement of microtubules during nuclear division. Pathogenic variants in KIF11 comprise primarily missense / nonsense variants, splicing variants, and small insertions and deletions. To date, large multi-exon deletions or duplications have not been reported for the KIF11 gene (Ostergaard et al. 2012; Hazan et al. 2012; Jones et al. 2014; Mirzaa et al. 2014; Robitaille et al. 2014). KIF11 variants were parentally inherited in over 60% of reported cases and there is inter-familial variability (Mirzaa et al. 2014). At least three patients with suspected disease causing variants were reportedly unaffected suggesting incomplete penetrance (Jones et al. 2013).
Clinical Sensitivity - Sequencing with CNV PGxome
A recent study identified KIF11 pathogenic variants in 12 of 15 families with syndromic autosomal-dominant microcephaly associated with lymphedema and / or chorioretinopathy (Ostergaard et al. 2012). Another study identified 5 de novo variants in 12 patients with syndromic autosomal-dominant microcephaly associated with lymphedema and / or chorioretinopathy (Mirzaa et al. 2014). These data suggest that sequencing for pathogenic variants in the KIF11 gene in patients suspected of having KIF11 related disorders (MCLMR, CDMMR, and FEVR) is highly specific and sensitive.
To date, large multi-exon deletions or duplications have not been reported for the KIF11 gene (Ostergaard et al. 2012; Hazan et al. 2012; Jones et al. 2014; Mirzaa et al. 2014; Robitaille et al. 2014).
Testing Strategy
This test provides full coverage of all coding exons of the KIF11 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).
Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).
Indications for Test
Patients with asymetric or bilateral lymphedema of the extremities that is not suspected to be caused by another condition or treatment such as cancer and cancer treatments or lymphandectomy. Patients with eye abnormalities, characteristic facial features, and mental retardation that also have lymphedema. Family members of patients suspected of having MLCRD, CDMMR, or FEVR.
Patients with asymetric or bilateral lymphedema of the extremities that is not suspected to be caused by another condition or treatment such as cancer and cancer treatments or lymphandectomy. Patients with eye abnormalities, characteristic facial features, and mental retardation that also have lymphedema. Family members of patients suspected of having MLCRD, CDMMR, or FEVR.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| KIF11 | 148760 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Microcephaly with or without Chorioretinopathy, Lymphedema, or Mental Retardation | AD | 152950 |
Citations
- Hazan F, Ostergaard P, Ozturk T, Kantekin E, Atlihan F, Jeffery S, Ozkinay F. 2012. A novel KIF11 mutation in a Turkish patient with microcephaly, lymphedema, and chorioretinal dysplasia from a consanguineous family. Am. J. Med. Genet. 158A: 16861689. PubMed ID: 22653704
- Jones GE, Ostergaard P, Moore AT, Connell FC, Williams D, Quarrell O, Brady AF, Spier I, Hazan F, Moldovan O, Wieczorek D, Mikat B, Petit F, Coubes C, Saul RA, Brice G, Gordon K, Jeffery S, Mortimer PS, Vasudevan PC, Mansour S. 2014. Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations. European Journal of Human Genetics 22: 881887. PubMed ID: 24281367
- Mirzaa GM, Enyedi L, Parsons G, Collins S, Medne L, Adams C, Ward T, Davitt B, Bicknese A, Zackai E, Toriello H, Dobyns WB, Christian S. 2014. Congenital microcephaly and chorioretinopathy due to de novo heterozygous KIF11 mutations: Five novel mutations and review of the literature. Am. J. Med. Genet. 164: 28792886. PubMed ID: 25115524
- Ostergaard P, Simpson MA, Mendola A, Vasudevan P, Connell FC, Impel A van, Moore AT, Loeys BL, Ghalamkarpour A, Onoufriadis A, Martinez-Corral I, Devery S, Leroy JG, van Laer L, Singer A, Bialer MG, McEntagart M, Quarrell O, Brice G, Trembath RC, Schulte-Merker S, Makinen T, Vikkula M, Mortimer PS, Mansour S, Jeffery S. 2012. Mutations in KIF11 Cause Autosomal-Dominant Microcephaly Variably Associated with Congenital Lymphedema and Chorioretinopathy. Am J Hum Genet 90: 356362. PubMed ID: 22284827
- Robitaille JM, Gillett RM, LeBlanc MA, Gaston D, Nightingale M, Mackley MP, Parkash S, Hathaway J, Thomas A, Ells A, Traboulsi EI, Hιon E, Roy M, Shalev S, Fernandez CV, MacGillivray C, Wallace K, Fahiminiya S, Majewski J, McMaster CR, Bedard K. 2014. PHenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by kif11 mutations. JAMA Ophthalmol 132: 13931399. PubMed ID: 25124931
- Valentine MT, Fordyce PM, Krzysiak TC, Gilbert SP, Block SM. 2006. Individual dimers of the mitotic kinesin motor Eg5 step processively and support substantial loads in vitro. Nature Cell Biology 8: 470476. PubMed ID: 16604065
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
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
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ORDER OPTIONS
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2) Select Additional Test Options
No Additional Test Options are available for this test.