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Arthrogryposis Multiplex Congenita via the ERGIC1 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
13081 ERGIC1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13081ERGIC181479 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 resulting in multiple 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). 

Neurogenic type AMC was first described in an Isareli Arab kindred consisting of 7 consanguineous families. Whole exome sequencing identified a homozygous missense variant in ERGIC1 in two affected individuals and additional segregation testing found this homozygous variant in at least eleven other affected individuals (Reinstein et al. 2018. PubMed ID: 28317099). Patients typically presented at birth with flexion contractures at the knees and elbows, with muscle hypotrophy and weakness around the involved joints. Neurologic and electrophysical examination showed a neuropathic type of arthrogryposis. An additional patient with arthrogryposis from a consanguineous family was also reported to be homozygous for an ERGIC1 missense variant. This patient showed restriction in the wrists and fingers and pes equinovarus deformity in the feet (Pehlivan et al. 2019. PubMed ID: 31230720). Genetic testing may aide in establishing a differential diagnosis and may assist reproductive planning.

Genetics

Pathogenic variants in the ERGIC1 gene are associated with autosomal recessive neurogenic type arthrogryposis multiplex congenita. To date, only missense variants have been reported (Pehlivan et al. 2019. PubMed ID: 31230720; Reinstein et al. 2018. PubMed ID: 28317099).  To date, all pathogenic variants have been inherited from a carrier parent. No structural variants have been reported.

The ERGIC1 gene encodes a putative transmembrane protein that is localized to the ER-Golgi intermediate compartment which is expressed in multiple tissues. Studies in regards to ERGIC1 protein function are limited and the mechanism by which ERGIC functions in membrane trafficking between the ER and Golgi is not understood. No mouse or zebrafish studies on ERGIC1 are available at this time; however, ERGIC1 has been cited as a non-essential gene for growth of human tissue culture cells (Online Gene Essentiality). No homozygous loss-of-function variants are reported in the gnomAD database, and ERGIC1 is overall relatively intolerant to loss-of-function variants (https://gnomad.broadinstitute.org/).

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 (Pehlivan et al. 2019. PubMed ID: 31230720; Reinstein et al. 2018. PubMed ID: 28317099). 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 ERGIC1 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. Targeted testing is indicated for family members of patients who have a known pathogenic variant in ERGIC1. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ERGIC1.

Gene

Official Gene Symbol OMIM ID
ERGIC1 617946
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Arthrogryposis multiplex congenita, neurogenic type AR 208100

Citations

  • Beecroft et al. 2018. PubMed ID: 29959180
  • Genome Aggregation Database.
  • Online Gene Essentiality (OGEE).
  • Pehlivan et al. 2019. PubMed ID: 31230720
  • Pergande et al. 2020. PubMed ID: 31680123
  • Reinstein et al. 2018. PubMed ID: 28317099

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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