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Centronuclear Myopathy-2, Autosomal Recessive via the BIN1 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
11109 BIN1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11109BIN181479 81479,81479 $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.

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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Autosomal recessive centronuclear myopathy (CNM2; OMIM 255200) has been found to be caused by mutations in the BIN1 gene (Nicot et al. Nature Genet 39:1134-1139, 2007).  Clinical and histological features of CNM2 include proximal muscle weakness and centrally placed nuclei with onset of weakness normally from birth to childhood (Nicot et al. Nature Genet 39:1134-1139, 2007).  Progression of muscle weakness appears to be slow.  Mild to severe contractures present at birth have been noted in one family.  Claeys et al. (Neurology 74:519-521, 2010) reported a CNM2 patient who had difficulty running and climbing stairs since childhood and first walked at age 3.5 years.  At 11 years of age diffuse muscle atrophy and progressive muscle weakness was noted in this patient.  Later, he was described as having scapular winging, hyperlordosis, a waddling gait, and Gower’s sign.  Weakness was prominent in proximal and distal muscles of all four limbs.  The patient was also described as being mildly dysmorphic with an elongated face, high-arched palate, and retrognathia.  The feet were high-arched and clubbed.  Evaluation of a muscle biopsy revealed centrally placed nuclei.  Unlike the patients described by Nicot et al. (Nature Genet 39:1134-1139, 2007), this patient had mild mental retardation.  An earlier report by Wallgren-Pettersson et al. (J Med Genet 32:673-679, 1995) noted that at least 12 families (21 patients) were known with centronuclear myopathy and with pedigrees compatible with autosomal recessive inheritance.  Onset of weakness in these patients varied from infancy (6 patients) to early childhood (7 patients) to ages 8 through 30 years (8 patients).  Muscle weakness was typically proximally.  Other clinical findings among these patients included ophthalmoplegia, ptosis, facial weakness, and feeding difficulties.

Genetics

Centronuclear myopathy is a genetically heterogeneous disorder.  One X-linked form and several autosomal dominant forms are known.  BIN1-related centronuclear myopathy is inherited as an autosomal recessive disorder.  Missense and nonsense mutations and are the only forms of pathogenic gene variants reported to date.  The reported mutations are believed to disrupt interaction of the BIN1 protein with dynamin 2, encoded by DNM2 (Nicot et al. Nature Genet 39:1134-1139, 2007).  BIN1 mRNA in skeletal muscle from patients with myotonic dystrophy has been shown to be affected by sequestration of the splicing regulator MBNL1 (Fugier et al. Nature Med 17:720-725, 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity may be high because all BIN1 mutations reported to date will be detectable by direct sequencing of genomic DNA. Clinical sensitivity is problematic to predict due to genetic heterogeneity of this disorder. From a cohort of 55 patients with histologically-diagnosed centronuclear myopathy, and with suspected autosomal recessive inheritance, three unrelated patients from three consanguineous families with BIN1 causative mutations were found (Nicot et al. Nature Genet 39:1134-1139, 2007).

Testing Strategy

This test provides full coverage of all coding exons of the BIN1 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 clinical features of CNM2 with centrally placed nuclei in muscle and autosomal recessive inheritance. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BIN1.

Gene

Official Gene Symbol OMIM ID
BIN1 601248
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Autosomal Recessive Centronuclear Myopathy AR 255200

Citations

  • Claeys KG, Maisonobe T, Bohm J, Laporte J, Hezode M, Romero NB, Brochier G, Bitoun M, Carlier RY, Stojkovic T. 2010. Phenotype of a patient with recessive centronuclear myopathy and a novel BIN1 mutation. Neurology 74: 519–521. PubMed ID: 20142620
  • Fugier et al. (2011) Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. Nature Med. 17:720-725. PubMed ID: 21623381
  • Nicot A-S, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier J-M, Biancalana V, Oldfors A, Mandel J-L, Laporte J. 2007. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nature Genetics 39: 1134–1139. PubMed ID: 17676042
  • Wallgren-Pettersson et al. (1995). The myotubular myopathies: differential diagnosis of the X linked recessive, autosomal dominant, and autosomal recessive forms and present state of DNA studies. J Med Genet 32:673-679  PubMed ID: 8544184

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.
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