Galloway-Mowat Syndrome (GAMOS) via the LAGE3 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
13089 LAGE3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13089LAGE381479 81479(x2) $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.

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

Clinical Features and Genetics

Clinical Features

Galloway-Mowat syndrome (GAMOS) is an extremely rare autosomal recessive disorder characterized by neurological impairments, developmental abnormalities and early-onset nephrotic syndrome (Colin et al. 2014. PubMed ID: 25466283; Jinks et al. 2015. PubMed ID: 26070982). The primary features are infantile onset of cerebellar atrophy, microcephaly and proteinuria.

Other features include, but are not limited to, hiatal hernia, seizures, dystonia, generalized hypotonia, and visual impairment. These features are variable among patients, and have overlapping presentations with other disorders. Genetic testing is essential for differential diagnosis.

Genetics

Galloway-Mowat syndrome represents a clinically and genetically heterogeneous group of autosomal recessive or X-linked disorders. To date, ten genes have been associated with Galloway-Mowat syndrome: WDR73, NUP107, NUP133, WDR4, TPRKB, OSGEP, TP53RK, LAGE3, GON7, and YRDC (Colin et al. 2014. PubMed ID: 25466283; Jinks et al. 2015. PubMed ID: 26070982; Braun et al. 2017. PubMed ID: 28805828; Braun et al. 2018. PubMed ID: 30179222; Braun et al. 2018. PubMed ID: 30079490; Arrondel et al. 2019. PubMed ID: 31481669). The LAGE3 gene is one of minor causative genes for the disease. LAGE3-related Galloway-Mowat syndrome is X-linked and to date, all reported patients are male.

Loss-of-function is the underlying mechanism of the LAGE3 gene for Galloway-Mowat syndrome.  To date, only two pathogenic missense substitutions and two truncating (splicing) variants in the LAGE3 gene have been reported (Human Gene Mutation Database). Large deletions and duplications have not been reported in this gene. Since LAGE3 is X-linked, de novo variants are presumably not uncommon as one has been reported (Baker et al. 2019. PubMed ID: 31069511).

LAGE3 alongside other four genes OSGEP, TPRKB, TP53RK and GON7 encode the subunits of the highly conserved KEOPS complex (Kinase, Endopeptidase and Other Proteins of small Size), which is essential for a universal chemical modification of tRNAs. LAGE3 has been cited as a conditional gene for growth of human tissue culture cells (Online Gene Essentiality, ogee.medgenius.info). The phenotype of microcephaly resulting in early lethality has been seen in CRISPR/Cas9 knockout in zebrafish and mice (Braun. 2017. PubMed ID: 28805828).

Clinical Sensitivity - Sequencing with CNV PGxome

Compared with WDR73, OSGEP and NUP107, LAGE3 is one of the minor causative genes for Galloway-Mowat syndrome. In a whole-exome sequencing study of patients with Galloway-Mowat syndrome, 3 of 91 (~3.2%) families were found to have pathogenic variants in LAGE3 (Braun et al. 2017. PubMed ID: 28805828).

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 LAGE3 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

Candidates for this test are patients with Galloway-Mowat syndrome (GAMOS). Targeted testing is indicated for family members of patients who have known pathogenic variants in the LAGE3 gene.

Gene

Official Gene Symbol OMIM ID
LAGE3 300060
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Galloway-Mowat Syndrome 2, X-linked XL 301006

Related Tests

Name
Galloway-Mowat Syndrome (GAMOS) Panel
Nephrotic Syndrome (NS)/Focal Segmental Glomerulosclerosis (FSGS) Panel

Citations

  • Arrondel et al. 2019. PubMed ID: 31481669
  • Baker et al. 2019. PubMed ID: 31069511
  • Braun et al. 2017. PubMed ID: 28805828
  • Braun et al. 2018. PubMed ID: 30179222
  • Braun et al. 2018. PubMed ID: 30079490
  • Colin et al. 2014. PubMed ID: 25466283
  • Genome Aggregation Database.
  • Human Gene Mutation Database (Biobase).
  • Jinks et al. 2015. PubMed ID: 26070982
  • Online Gene Essentiality (OGEE).

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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