Brown-Vialetto-Van Laere Syndrome 1 and Fazio-Londe Disease (Progressive Bulbar Palsy With or Without Sensorineural Deafness) via the SLC52A3 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
8711 SLC52A3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8711SLC52A381479 81479 $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.

For Reflex to PGxome pricing click here.

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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Brown-Vialetto-van Laere syndrome and Fazio-Londe disease are rare neurologic disorders caused by variants in the SLC52A3 (C20orf54) gene (OMIM 613350). Progressive bulbar palsy with sensorineural deafness, also called Brown-Vialetto-van Laere syndrome (BVVLS, OMIM 211530), is a disorder with clinical findings of bulbar palsy, neurological deterioration, muscle weakness, respiratory insufficiency, and early death. Onset of symptoms has been reported in the first decade of life (Green et al. Am J Hum Genet 86:485-489, 2010). Sensorineural deafness was also found to be a common feature, but more often in patients with later onset. Fazio-Londe disease (OMIM 211500) is a progressive bulbar palsy with onset in childhood that presents with hypotonia and respiratory insufficiency due to diaphragmatic paralysis (Bosch et al. J Inherit Metab Dis 34:159-164, 2011). The Fazio-Londe disease patients described by Bosch et al. (2011) displayed plasma acylcarnitine and urine organic acid profiles suggestive of a mild form of the multiple acyl-CoA dehydrogenation defect (MADD). However, further biochemical testing revealed a profound flavin deficiency in spite of a normal dietary riboflavin intake. Brown-Vialetto-van Laere syndrome and Fazio-Londe disease are believed to represent variable presentations of a single disorder (Dipti et al. Brain Dev 27:443–446, 2005).

Genetics

BVVLS and Fazio-Londe disease are inherited as autosomal recessive disorders. By two different approaches, the SLC52A3 gene (OMIM 613350) was identified as the cause of Brown-Vialetto-van Laere syndrome (Johnson et al. Am J Hum Genet 87:567-569, 2010; Green et al. Am J Hum Genet 86:485-489, 2010). The SLC52A3 gene encodes a human homolog of the rat riboflavin transporter, and it is thought to play a role in riboflavin transport in humans as well (Green et al. Am J Hum Genet 86:485-489, 2010; Bosch et al. J Inherit Metab Dis 34:159-164, 2011). A small number of patients worldwide have thus far been documented. SLC52A3 variants types reported in patients include missense, nonsense, splicing, and frameshift.

Clinical Sensitivity - Sequencing with CNV PGxome

Brown-Vialetto-van Laere syndrome and Fazio-Londe disease are both rare disorders, and clinical sensitivity cannot yet be estimated. Analytical sensitivity should be high because all variants thus far reported are detectable by sequencing genomic DNA.

Testing Strategy

This test provides full coverage of all coding exons of the SLC52A3 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with clinical features consistent with Brown-Vialetto-van Laere syndrome or Fazio-Londe disease and demonstrated autosomal recessive inheritance. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC52A3.

Gene

Official Gene Symbol OMIM ID
SLC52A3 613350
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Brown-Vialetto-Van Laere Syndrome AR 211530
Fazio-Londe Disease AR 211500

Related Test

Name
Brown-Vialetto-Van Laere Syndrome 2 and Fazio-Londe Disease (Progressive Bulbar Palsy with or without Sensorineural Deafness) via the SLC52A2 Gene

Citations

  • Bosch AM, Abeling NGGM, IJlst L, Knoester H, Pol WL, Stroomer AEM, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR. 2010. Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment. Journal of Inherited Metabolic Disease 34: 159–164. PubMed ID: 21110228
  • Dipti S, Childs A-M, Livingston JH, Aggarwal AK, Miller M, Williams C, Crow YJ. 2005. Brown–Vialetto–Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio-Londe disease. Brain and Development 27: 443–446. PubMed ID: 16122634
  • Green P, Wiseman M, Crow YJ, Houlden H, Riphagen S, Lin J-P, Raymond FL, Childs A-M, Sheridan E, Edwards S, Josifova DJ. 2010. Brown-Vialetto-Van Laere Syndrome, a Ponto-Bulbar Palsy with Deafness, Is Caused by Mutations in C20orf54. The American Journal of Human Genetics 86: 485–489. PubMed ID: 20206331
  • Johnson, J. O., et.al. (2010). "Exome sequencing in Brown-Vialetto-van Laere syndrome." Am J Hum Genet 87(4): 567-9; author reply 569-70. PubMed ID: 20920669

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.

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

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ORDER OPTIONS

View Ordering Instructions

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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.

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