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Fetal Akinesia Deformation Sequence 4 via the NUP88 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
13083 NUP88 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13083NUP8881479 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

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


  • 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).

FADS 4 has been reported in two unrelated families to date. In one family, 4 affected pregnancies were reported in which two of the fetuses were found to be homozygous for a missense variant in NUP88. Clinical features for these pregnancies included intrauterine demise in 2 pregnancies, decreased fetal movements, arthrogryposis multiplex congenita (contractures of fingers, hands, elbow, and feet), muscle atrophy, polyhydramnios and ascites, high arched palate, absent stomach bubble, severe respiratory distress, and other dysmorphic features (Bonnin et al. 2018. PubMed ID: 30543681). In an additional family, compound heterozygous variants in NUP88 were found in one affected fetus with similar features to the previous family (Bonnin et al. 2018. PubMed ID: 30543681). Genetic testing may aide in establishing a differential diagnosis and may assist reproductive planning.


Pathogenic variants in the NUP88 gene are associated with autosomal recessive fetal akinesia deformation sequence (FADS) 4. A missense variant, a nonsense variant, and an in-frame deletion have been reported in 3 individuals with fetal akinesia deformation sequence from 2 families (Bonnin et al. 2018. PubMed ID: 30543681). The 3 individuals included one individual with compound heterozygous NUP88 pathogenic variants and two siblings who were homozygous for a NUP88 pathogenic missense variant. To date, all pathogenic variants have been inherited from a carrier parent. No structural variants have been reported.

The NUP88 gene encodes a nuceloporin protein which is a component of the nuclear pore complex (NPC). The NPC is necessary for all trafficking between the nucleus and cytoplasm and NUP88 is found in sub-complexes on both the nuclear and cytoplasmic sides. On the nuclear side of the complex, NUP88 has been shown to bind the intermediate filament protein lamin A (Lussi et al. 2011. PubMed ID: 21289091). Disruption of NUP88 in zebrafish resulted in micrognathia, smaller head and eyes, distortion of the body axis, and aplastic swim bladder which corresponds with features seen in human fetuses with FADS (Bonnin et al. 2018. PubMed ID: 30543681). NUP88 has been cited as a conditional gene for growth of human tissue culture cells (Online Gene Essentiality). No homozygous loss-of-function variants are reported in the gnomAD database (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 (Bonnin et al. 2018. PubMed ID: 30543681). 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 NUP88 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.

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 a known pathogenic variant in NUP88. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NUP88.


Official Gene Symbol OMIM ID
NUP88 602552
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Fetal akinesia deformation sequence 4 AR 618393


  • Beecroft et al. 2018. PubMed ID: 29959180
  • Bonnin et al. 2018. PubMed ID: 30543681
  • Genome Aggregation Database.
  • Lussi et al. 2011. PubMed ID: 21289091
  • Online Gene Essentiality (OGEE).
  • Pergande et al. 2020. PubMed ID: 31680123


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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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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