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Arthrogryposis Multiplex Congenita via the UNC50 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
13327 UNC50 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13327UNC5081479 81479,81479 $890 Order Options and Pricing

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).

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

Fetal akinesia (FA) describes a clinical syndromic entity characterized by reduced or absent fetal movements with additional phenotypic abnormalities. These secondary defects may include intrauterine growth restriction (IUGR), craniofacial dysmorphic features (cleft palate or retromicrognathia), limb pterygia, pulmonary hypoplasia, and arthrogryposis. This group of disorders contains several overlapping conditions ranging from distal arthrogryposis, multiple pterygium syndrome, arthrogryposis multiplex congenita (AMC), to the more severe lethal congenital contracture syndrome and fetal akinesia deformation sequence (FADS) (Beecroft et al. 2018. PubMed ID: 29959180; Pergande et al. 2020. PubMed ID: 31680123).

AMC is defined by congenital, non-progressive contractures in more than two joints and in multiple body areas. These contractures and reduced fetal movement can lead to secondary polyhydramnios or fetal hydrops. The underlying defect can be genetic or environmental. Causes can include muscle disorders, neurological disorders, connective tissue disorders, fetal vascular compromise, uterine space limitations, and maternal disease or drug use. The overall incidence of AMC ranges from 1/3,000 to 1/5,000 live births (Beecroft et al. 2018. PubMed ID: 29959180; Pergande et al. 2020. PubMed ID: 31680123).

One family has been reported so far with a pathogenic frameshift variant in UNC50. The affected pregnancy presented with bilateral club foot, bilateral flexion of elbows, hips and knees, bilateral extended wrists, cervical hyperextension and diffuse subcutaneous, and edema associated with muscle atrophy of limbs (Abiusi et al. 2017. PubMed ID: 29016857). The pregnancy ended in a stillborn male at 28 weeks gestation. The affected male child was found to be homozygous for the frameshift variant, while unaffected parents and unaffected siblings were heterozygous or carried the wild type allele. Genetic testing may aid in establishing a differential diagnosis and may assist reproductive planning.

Genetics

Pathogenic variants in the UNC50 gene are associated with autosomal recessive arthrogryposis multiplex congenita. Thus far, only one frameshift variant in the last exon of the gene has been reported to be pathogenic (Abiusi et al. 2017. PubMed ID: 29016857).  This variant was knocked-in to C. elegans and the animals displayed an uncoordinated phenotype, similar to unc-50 null mutants. To date, all pathogenic variants have been inherited from a carrier parent. No structural variants have been reported.

The UNC50 gene encodes a transmembrane protein that is localized to the Golgi apparatus. In C. elegans, unc-50 mutant animals display slow and abnormal locomotion, called an ‘uncoordinated phenotype’, for which the gene was originally named. Inactivation of the unc-50 gene eliminates the expression of heteromeric acetylcholine receptors (AChR) at the neuromuscular junction. UNC50 has been cited as a non-essential gene for growth of human tissue culture cells (Online Gene Essentiality).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity is difficult to estimate, as to date, a limited number of cases have been described in the literature (Abiusi et al. 2017. PubMed ID: 29016857). Analytical sensitivity should be high as all pathogenic variants reported to date are detectable by sequencing.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the UNC50 gene plus 10 bases flanking noncoding DNA in all available transcripts in addition to 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 clinical features consistent with a diagnosis of arthrogryposis multiplex congenita (AMC) or fetal akinesia deformation sequence (FADS). Targeted testing is indicated for family members of patients who have known pathogenic variants in UNC50. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in UNC50.

Gene

Official Gene Symbol OMIM ID
UNC50 617826
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Abiusi et al. 2017. PubMed ID: 29016857
  • Beecroft et al. 2018. PubMed ID: 29959180
  • Online Gene Essentiality (OGEE).
  • Pergande et al. 2020. PubMed ID: 31680123

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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