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Hypomyelination and Congenital Cataract (HCC) via the FAM126A Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11317 FAM126A 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11317FAM126A81479 81479(x2) $890 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 backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Hypomyelination and congenital cataract (HCC) is a rare autosomal recessive white matter disorder. HCC is clinically characterized by the unique combination of bilateral congenital cataract (which is evident in the first year of life), and primary hypomyelination (myelin deficiency) of the central and peripheral nervous system. This is followed by secondary progressive neurodegenerative changes with spasticity, cerebellar ataxia, and mild-to-moderate cognitive impairment (Biancheri et al. 2011; Biancheri et al. 2007; Traverso et al. 2013).

Genetics

HCC is an autosomal recessive disorder caused by deficiency of the membrane protein Hyccin, which is encoded by the FAM126A (previously known as DRCTNNB1A) gene located on chromosome 7p21.3-p15.3 (Kawasoe et al. 2000). Mouse mutant studies indicated that hyccin is predominantly expressed in the neurons of the central nervous system (CNS), but not in the myelinating cells and has a role in neuron-to-glia signaling to initiate or maintain myelination (Gazzerro et al. 2012; Zara et al. 2006). So far, about 10 causative FAM126A sequence variations (missense, nonsense, splicing, small insertions and deletions) have been reported in HCC (Human Gene Mutation Database). Functional studies indicated that missense mutations cause a milder phenotype compared to splice-site mutations and deletions, which cause a severe HCC phenotype, including peripheral nervous system involvement (Traverso et al. 2013). Genetic analyses in a large consanguineous family from Eastern Turkey revealed that all affected individuals (5) had a large intragenic FAM126A deletion, and not all the patients had congenital cataract, which indicates that congenital cataract should not be considered a prerequisite for the diagnosis of HCC (Ugur and Tolun 2008). Biochemical or molecular genetic testing should be included in the differential diagnosis of HCC and other hypomyelinating forms (such as Pelizaeus-Merzbacher disease, which is caused by mutations in the PLP1 gene) (Traverso et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

In three different studies, FAM126A mutations were identified in all Hypomyelination and congenital cataract (HCC) affected patients (Zara et al. 2006; Traverso et al. 2013; Biancheri et al. 2011). These studies suggest a high clinical sensitivity. Analytical sensitivity should also be high because majority of mutations reported are detectable by direct sequencing of genomic DNA. Only one gross deletion in FAM126A has been reported (Ugur and Tolun 2008).

Testing Strategy

This test provides full coverage of all coding exons of the FAM126A 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

Candidates for this test are patients with symptoms consistent with hypomyelination and congenital cataract (HCC), and family members of patients with known mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FAM126A.

Gene

Official Gene Symbol OMIM ID
FAM126A 610531
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hypomyelination And Congenital Cataract AR 610532

Citations

  • Biancheri R, Zara F, Bruno C, Gazzerro E, Rossi A, Knaap MS Van der, Minetti C. 2011. Hypomyelination and Congenital Cataract. 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: 20301737
  • Biancheri R, Zara F, Bruno C, Rossi A, Bordo L, Gazzerro E, Sotgia F, Pedemonte M, Scapolan S, Bado M, Uziel G, Bugiani M, et al. 2007. Phenotypic characterization of hypomyelination and congenital cataract. Ann. Neurol. 62: 121–127. PubMed ID: 17683097
  • Biancheri R, Zara F, Rossi A, Mathot M, Nassogne MC, Yalcinkaya C, Erturk O, Tuysuz B, Rocco M Di, Gazzerro E, others. 2011. Hypomyelination and congenital cataract: broadening the clinical phenotype. Archives of neurology 68: 1191–1194. PubMed ID: 21911699
  • Gazzerro E, Baldassari S, Giacomini C, Musante V, Fruscione F, Padula V La, Biancheri R, Scarfì S, Prada V, Sotgia F, Duncan ID, Zara F, et al. 2012. Hyccin, the molecule mutated in the leukodystrophy hypomyelination and congenital cataract (HCC), is a neuronal protein. PLoS ONE 7: e32180. PubMed ID: 22461884
  • Human Gene Mutation Database (Bio-base).
  • Kawasoe T, Furukawa Y, Daigo Y, Nishiwaki T, Ishiguro H, Fujita M, Satoh S, Miwa N, Nagasawa Y, Miyoshi Y, Ogawa M, Nakamura Y. 2000. Isolation and characterization of a novel human gene, DRCTNNB1A, the expression of which is down-regulated by beta-catenin. Cancer Res. 60: 3354–3358. PubMed ID: 10910037
  • Traverso M, Assereto S, Gazzerro E, Savasta S, Abdalla EM, Rossi A, Baldassari S, Fruscione F, Ruffinazzi G, Fassad MR, El Beheiry A, Minetti C, et al. 2013. Novel FAM126A mutations in hypomyelination and congenital cataract disease. Biochem. Biophys. Res. Commun. 439: 369–372. PubMed ID: 23998934
  • Ugur SA, Tolun A. 2008. A deletion in DRCTNNB1A associated with hypomyelination and juvenile onset cataract. Eur. J. Hum. Genet. 16: 261–264. PubMed ID: 17928815
  • Zara F, Biancheri R, Bruno C, Bordo L, Assereto S, Gazzerro E, Sotgia F, Wang XB, Gianotti S, Stringara S, Pedemonte M, Uziel G, et al. 2006. Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract. Nat. Genet. 38: 1111–1113. PubMed ID: 16951682

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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