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Marinesco-Sjogren Syndrome via the SIL1 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
SIL1 81405 81405,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11667SIL181405 81405,81479 $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.


Genetic Counselors


  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive multisystem disorder, which is characterized by cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development (Anttonen and Lehesjoki 2010; Anttonen et al. 2005; Horvers et al. 2013; Krieger et al. 2013). Cataracts progress very rapidly and typically require surgery to restore lens transparency in the first decade of life. Life expectancy of MSS affected individuals appears to be near normal. However, the majority of the affected adults are handicapped (Anttonen and Lehesjoki 2010).


SIL1 (also known as BAP, BiP-Associated Protein) is the only gene that has been documented to be involved in MSS. MSS is an autosomal recessive disorder with a carrier frequency of 1 in 96 in Finland (Anttonen and Lehesjoki 2010). SIL1 encodes an endoplasmic reticulum (ER) resident co-chaperone, which acts as a nucleotide exchange factor for the heat-shock protein 70 (HSP70) chaperone HSPA5 (also known as BiP- immunoglobulin heavy chain binding protein). BiP is reported to be the key regulator in the folding and assembly of nascent polypeptide chains in the ER (Senderek et al. 2005; Anttonen et al. 2005 Weitzmann et al. 2006; Howes et al. 2012; Krieger et al. 2013). Due to mutations in SIL1, SIL1-HSPA5 interaction is disturbed and leads to protein misfolding, which may be the mechanism of molecular pathology in Marinesco-Sjögren syndrome (Anttonen et al. 2005). Subcellular localization studies of the product of SIL1 missense mutations indicated that mutant proteins aggregates within the ER may contribute to MSS pathogenesis (Anttonen et al. 2008; Howes et al. 2012). ER dysfunction in MSS suggests a role for this organelle in multisystem disorders (Senderek et al. 2005). SIL1 mutation analysis in children suspected with inherited ataxias would be helpful in the early diagnosis of MSS, and in possible interventions such as cataract surgery (Horvers et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

Krieger et al. reported that the SIL1 mutation detection rate is 60% (15/25) among patients with the characteristic Marinesco-Sjögren syndrome (MSS) triad (ataxia, cataracts, myopathy) (Krieger et al. 2013). Some of the MSS cases that are negative for SIL1 sequencing could be due to deletions that cannot be detected via sequencing rather than locus heterogeneity (Takahata et al. 2010). So far, three gross deletions have been reported in SIL1 gene (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the SIL1 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

All patients with symptoms suggestive of Marinesco-Sjögren syndrome are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SIL1.


Official Gene Symbol OMIM ID
SIL1 608005
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Marinesco-Sjogren Syndrome AR 248800


  • Anttonen A-K, Lehesjoki A-E. 2010. Marinesco-Sjögren Syndrome. 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: 20301371
  • Anttonen A-K, Mahjneh I, Hämäläinen RH, Lagier-Tourenne C, Kopra O, Waris L, Anttonen M, Joensuu T, Kalimo H, Paetau A, Tranebjaerg L, Chaigne D, et al. 2005. The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone. Nat. Genet. 37: 1309–1311. PubMed ID: 16282978
  • Anttonen A-K, Siintola E, Tranebjaerg L, Iwata NK, Bijlsma EK, Meguro H, Ichikawa Y, Goto J, Kopra O, Lehesjoki A-E. 2008. Novel SIL1 mutations and exclusion of functional candidate genes in Marinesco-Sjögren syndrome. Eur. J. Hum. Genet. 16: 961–969. PubMed ID: 18285827
  • Horvers M, Anttonen AK, Lehesjoki AE, Morava E, Wortmann S, Vermeer S, Warrenburg BP van de, Willemsen MA. 2013. Marinesco-Sjögren syndrome due to SIL1 mutations with a comment on the clinical phenotype. Eur. J. Paediatr. Neurol. 17: 199–203. PubMed ID: 23062754
  • Howes J, Shimizu Y, Feige MJ, Hendershot LM. 2012. C-terminal mutations destabilize SIL1/BAP and can cause Marinesco-Sjögren syndrome. J. Biol. Chem. 287: 8552–8560. PubMed ID: 22219183
  • Human Gene Mutation Database (Bio-base).
  • Krieger M, Roos A, Stendel C, Claeys KG, Sonmez FM, Baudis M, Bauer P, Bornemann A, Goede C de, Dufke A, Finkel RS, Goebel HH, et al. 2013. SIL1 mutations and clinical spectrum in patients with Marinesco-Sjogren syndrome. Brain 136: 3634–3644. PubMed ID: 24176978
  • Senderek J, Krieger M, Stendel C, Bergmann C, Moser M, Breitbach-Faller N, Rudnik-Schöneborn S, Blaschek A, Wolf NI, Harting I, North K, Smith J, et al. 2005. Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy. Nat. Genet. 37: 1312–1314. PubMed ID: 16282977
  • Takahata T, Yamada K, Yamada Y, Ono S, Kinoshita A, Matsuzaka T, Yoshiura K, Kitaoka T. 2010. Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjögren syndrome. J. Hum. Genet. 55: 142–146. PubMed ID: 20111056
  • Weitzmann A, Volkmer J, Zimmermann R. 2006. The nucleotide exchange factor activity of Grp170 may explain the non-lethal phenotype of loss of Sil1 function in man and mouse. FEBS Lett. 580: 5237–5240. PubMed ID: 16962589


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